AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors ...AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.展开更多
Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been propos...Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.展开更多
INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approxim...INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approximately for more than 40 percent ofthe total number in the world.HCC has become thesecond major cause of death for cancer in展开更多
The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates...The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.展开更多
BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is...BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.展开更多
To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and correspo...To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and corresponding subsoil samples)were collected from the five representative land-use patterns.Inductively coupled plasma mass spectrometry(ICP-MS),Atomic fluorescence spectrometry(AFS),and Inductively coupled plasma optical emission spectrometry(ICP-OES)were used to determine the content of PTEs(As,Cd,Hg,Cu,Cr,Ni,Pb,Zn,Co,Mo,Sb,and V).Correlation analysis and factor analysis were used to determine the source of PTEs.Geo-accumulation index(I_(geo)),hazard quotient(HQ),and total carcinogenic risk index(TR)were used to measure the PTEs contamination and its relative health impacts.Results showed that the average values of 12 PTEs in topsoil were higher than the Hainan soil geochemical baseline,showing different degrees of PTEs accumulation effect.The concentration of PTEs in the topsoil was lower than those in the subsoil except for Cd and Hg.The I_(geo)revealed that the major accumulated element in soils was As followed by Mo.Source apportionment suggested that parent materials and agricultural practices were the dominant factors for PTEs accumulation in the topsoil.Noncarcinogenic risks of soil samples from five land-use patterns presented a trend of paddy field>dry field>woodland>orchard>garden plot.However,the HQ values of 12 PTEs were less than the recommended limit of HQ=1,representing that there are no non-carcinogenic risks of PTEs for children and adults in the study area.The TR values are within 6.95×10^(-6)-1.38×10^(-5),which corresponds to the low level.Therefore the PTEs in the agricultural soil of the study area show little influence on the health status of the local population.展开更多
To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Healt...To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.展开更多
Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic d...Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.展开更多
Mycotoxins are secondary toxic metabolites synthesized by numerous filamentous fungi including members of the genus Fusarium,Penicillium,Drechslera,Aspergillus,Claviceps,Monascum,Alternaria,Cephalosporium,Nigrospora,a...Mycotoxins are secondary toxic metabolites synthesized by numerous filamentous fungi including members of the genus Fusarium,Penicillium,Drechslera,Aspergillus,Claviceps,Monascum,Alternaria,Cephalosporium,Nigrospora,and Trichoderma.Among them,Aspergillus and Fusarium species are major plant pathogens recognized to induce infection and produce mycotoxins in food crops.More than 400 mycotoxins have been documented and among them,aflatoxin,fumonisins,trichothecenes,zearalenone,ochratoxin A,citrinin,ergot alkaloids,and patulin are the most prominent compounds linked to a variety of human and animal health disorders.Genus Fusarium and Aspergillus belong to a saprophytic group,which can infect and contaminate many crops at pre and post-harvest stages.Mycotoxins can have a variety of negative effects on health in both humans and animals.Mycotoxins and their metabolites can cause severe acute poisoning,which can result in death,as well as long-term negative health effects,such as cancer and immune-suppressive disorders in living beings(animals and humans).Mycotoxin contamination of agricultural goods has gained global significance,due to its toxic effects on living beings,as well as its importance to international trade.Our objective is to provide a consolidated information on the potential mycotixs in food grains and their significant impact on the health of the human beings.展开更多
The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matte...The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) where there is a lack of information on the carcinogenic and non-carcinogenic risk to human health associated with the exposure of populations in the Tongon area to these pollutants. The general objective of this study is to evaluate the level of contamination of PM<sub>10</sub>;PM<sub>2.5</sub> by heavy metals and their impact on the health of populations exposed to these pollutants in the Tongon gold mine area. The sampling and measurement of suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) were done using a MiniVol TAS passive air sampler. Heavy metal concentrations were determined by inductively coupled plasma mass spectroscopy (Nex ION 2000 ICP-MS, USA). The results indicate that the average concentrations of suspended particles (PM<sub>2.5</sub> and PM<sub>10</sub>) obtained are all above the recommended exposure limits. In addition, among the heavy metals contained in the suspended particles, the concentrations of arsenic and nickel are high and all above the standard limit values. The assessment of the health risks related to the inhalation of PM<sub>10</sub> particles reveals that their inhalation over a long period could cause a carcinogenic risk.展开更多
This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant...This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.展开更多
Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameter...Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameters. Methods: COX-1 and COX-2 were detected in 56 ex- tra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avi- din-biotin complex using isozyme selective antibod- ies. Results: There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and non- cancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepat- ic cholangiocarcinomas (86%, 48/56) was signifi- cantly higher than their matched tissues (39%, 12/ 31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra- hepatic cholangiocarcinoma was related to the metas- tasis of lymph nodes, distant organs or tissues (P< 0.05) as well as the degree of tumour differentiation (P<0.05). Conclusions: The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.展开更多
Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutag...Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutagens").Control ofproliferation and differentiation within andbetween tissues is mediated by展开更多
AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly sel...AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly selected from 10 counties withinFujian Province.All subjects were localresidents who had been living in Fujian Provincefor more than 20 years,within the age group of45-74 years.Trained interviewers conductedface-to-face interviews with a standardizedquestionnaire,which covered the frequency andamount of food intake,dietary habit,tobaccoand alcohol consumption and history of chronicgastric diseases.Univariate and multivariateanalyses were performed using Epi-info and SASstatistical packages,respectively.RESULTS A significant correlation betweenmonthly consumption of fish sauce and mortalityof gastric cancer was found.Pearson’scoefficient of correlation was statisticallysignificant with r=0.7356 for males,r=0.5246for females(P【0.01).In the multivariateanalysis,consumption of fish sauce still showedan association with the risk of gastric cancer.No significant positive correlation betweenesophagus cancer,liver cancer,colon cancerand consumption of fish sauce were observed.CONCLUSION Long-term intake of fish saucemay be related to high mortality of gastriccancer.Consumption of fish sauce might be oneof important and unique etiologic factors ofgastric cancer in Fujian Province.Furtherstudies are needed to confirm this ecologicalstudy.展开更多
INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×1...INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver展开更多
INTRODUCTIONThe field of gastrointestinal hormones has expanded at a dizzying rate[1-4].Gastrointestinal hormones as regulatory peptides that appear to be major components of bodily integration and have important regu...INTRODUCTIONThe field of gastrointestinal hormones has expanded at a dizzying rate[1-4].Gastrointestinal hormones as regulatory peptides that appear to be major components of bodily integration and have important regulatory actions on physioligical function of the gastrointestinal tract .The successful isolation of some gastrointestinal hormones and the development of sensitive methods for their detection have led to the unexpected finding that they also exist in the brain .展开更多
Objective To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. Methods Meta...Objective To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. Methods Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann Whitney nonparametric U-tests and multiple linear regression. Results The concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 gg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 p.g/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (〈500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens. Conclusion Both mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.展开更多
Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). Methods Male and femal...Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). Methods Male and female B6C3F1 mice were exposed, through inhalation, intravenous administration and diet, to 0.5 ppm of ozone, 1.0 mg/kg of NNK and 5000 ppm of DBP, individually and in combination for 16 and 32 weeks. Results No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment. Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks. Conclusion Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions, they induce oviductal carcinomas in B6C3F1 mice.展开更多
Color is the main attraction of any fabric. No matter how excellent its constitution, if unsuitably colored it is bound to be a failure as a commercial fabric. Manufacture and use of synthetic dyes for fabric dyeing h...Color is the main attraction of any fabric. No matter how excellent its constitution, if unsuitably colored it is bound to be a failure as a commercial fabric. Manufacture and use of synthetic dyes for fabric dyeing has therefore become a massive industry today. In fact the art of applying color to fabric has been known to mankind since 3500 BC. WH Perkins in 1856 discovered the use of synthetic dyes. Synthetic dyes have provided a wide range of colorfast, bright hues. However their toxic nature has become a cause of grave concern to environmentalists. Use of synthetic dyes has an adverse effect on all forms of life. Presence of sulphur, naphthol, vat dyes, nitrates, acetic acid, soaps, enzymes chromium compounds and heavy metals like copper, arsenic, lead, cad- mium, mercury, nickel, and cobalt and certain auxiliary chemicals all collectively make the textile effluent highly toxic. Other harmful chemicals present in the water may be formaldehyde based dye fixing agents, chlorinated stain removers, hydro carbon based softeners, non bio degradable dyeing chemicals. These organic materials react with many disinfectants especially chlorine and form by products (DBP’S) that are often carcinogenic and therefore undesirable. Many of these show allergic reactions. The colloidal matter present along with colors and oily scum increases the turbidity, gives the water a bad appearance and foul smell and prevents the penetration of sunlight necessary for the process of photosynthesis. This in turn interferes with the Oxygen transfer mechanism at air water interface which in turn interferes with marine life and self purification process of water. This effluent if allowed to flow in the fields’ clogs the pores of the soil resulting in loss of soil productivity. If allowed to flow in drains and rivers it effects the quality of drinking water in hand pumps making it unfit for human consumption. It is important to remove these pollutants from the waste waters before their final disposal.展开更多
The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experim...The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.展开更多
基金Supported by The PhD University Grant program"Clinical and Experimental Research Methodologies in Oncology"provided by the Faculty of Medicine and Psychology University of Rome"La Sapienza"to Lorenzon LMIUR and AIRC-Associazione Italiana per la Ricerca sul Cancro(IG 10272),Italy
文摘AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.
文摘Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.
文摘INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approximately for more than 40 percent ofthe total number in the world.HCC has become thesecond major cause of death for cancer in
文摘The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
文摘BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.
基金supported by Open Foundation of the Key Laboratory of Coupling Process and Effect of Natural Resources Elements(No.2023KFKTB001)the Science&Technology Fundamental Resources Investigation Program(2022FY101800)+2 种基金the National Nonprofit Institute Research Grant of IGGE(AS2023D01)the projects of the China Geological Survey(DD20230309 and DD20190305)the National Natural Science Foundation of China(42002105)。
文摘To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and corresponding subsoil samples)were collected from the five representative land-use patterns.Inductively coupled plasma mass spectrometry(ICP-MS),Atomic fluorescence spectrometry(AFS),and Inductively coupled plasma optical emission spectrometry(ICP-OES)were used to determine the content of PTEs(As,Cd,Hg,Cu,Cr,Ni,Pb,Zn,Co,Mo,Sb,and V).Correlation analysis and factor analysis were used to determine the source of PTEs.Geo-accumulation index(I_(geo)),hazard quotient(HQ),and total carcinogenic risk index(TR)were used to measure the PTEs contamination and its relative health impacts.Results showed that the average values of 12 PTEs in topsoil were higher than the Hainan soil geochemical baseline,showing different degrees of PTEs accumulation effect.The concentration of PTEs in the topsoil was lower than those in the subsoil except for Cd and Hg.The I_(geo)revealed that the major accumulated element in soils was As followed by Mo.Source apportionment suggested that parent materials and agricultural practices were the dominant factors for PTEs accumulation in the topsoil.Noncarcinogenic risks of soil samples from five land-use patterns presented a trend of paddy field>dry field>woodland>orchard>garden plot.However,the HQ values of 12 PTEs were less than the recommended limit of HQ=1,representing that there are no non-carcinogenic risks of PTEs for children and adults in the study area.The TR values are within 6.95×10^(-6)-1.38×10^(-5),which corresponds to the low level.Therefore the PTEs in the agricultural soil of the study area show little influence on the health status of the local population.
基金supported from the National Key Research and Development Program of China(No.2022YFF1302901)the Key Laboratory Construction Project of Guangxi(No.19-185-7)the Foundation for Hebei Education Department(No.2022QNJS05).
文摘To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.
基金This work was supported by the Natural Science Foundation of China(Nos.81870747,82170916)Clinical Medicine Plus X–Young Scholars Project(PKU2021LCXQ003)the Fundamental Research Funds for the Central Universities(BMU2021YJ001).
文摘Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.
基金This paper is contribution number 22-218-J from the Kansas State University Agricultural Experiment Station.All the authors are thankful to PRS editorial team(Publica-tion Review Service)for technical support during the writ-ing of this review article in an effective manner.
文摘Mycotoxins are secondary toxic metabolites synthesized by numerous filamentous fungi including members of the genus Fusarium,Penicillium,Drechslera,Aspergillus,Claviceps,Monascum,Alternaria,Cephalosporium,Nigrospora,and Trichoderma.Among them,Aspergillus and Fusarium species are major plant pathogens recognized to induce infection and produce mycotoxins in food crops.More than 400 mycotoxins have been documented and among them,aflatoxin,fumonisins,trichothecenes,zearalenone,ochratoxin A,citrinin,ergot alkaloids,and patulin are the most prominent compounds linked to a variety of human and animal health disorders.Genus Fusarium and Aspergillus belong to a saprophytic group,which can infect and contaminate many crops at pre and post-harvest stages.Mycotoxins can have a variety of negative effects on health in both humans and animals.Mycotoxins and their metabolites can cause severe acute poisoning,which can result in death,as well as long-term negative health effects,such as cancer and immune-suppressive disorders in living beings(animals and humans).Mycotoxin contamination of agricultural goods has gained global significance,due to its toxic effects on living beings,as well as its importance to international trade.Our objective is to provide a consolidated information on the potential mycotixs in food grains and their significant impact on the health of the human beings.
文摘The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) where there is a lack of information on the carcinogenic and non-carcinogenic risk to human health associated with the exposure of populations in the Tongon area to these pollutants. The general objective of this study is to evaluate the level of contamination of PM<sub>10</sub>;PM<sub>2.5</sub> by heavy metals and their impact on the health of populations exposed to these pollutants in the Tongon gold mine area. The sampling and measurement of suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) were done using a MiniVol TAS passive air sampler. Heavy metal concentrations were determined by inductively coupled plasma mass spectroscopy (Nex ION 2000 ICP-MS, USA). The results indicate that the average concentrations of suspended particles (PM<sub>2.5</sub> and PM<sub>10</sub>) obtained are all above the recommended exposure limits. In addition, among the heavy metals contained in the suspended particles, the concentrations of arsenic and nickel are high and all above the standard limit values. The assessment of the health risks related to the inhalation of PM<sub>10</sub> particles reveals that their inhalation over a long period could cause a carcinogenic risk.
文摘This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.
文摘Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameters. Methods: COX-1 and COX-2 were detected in 56 ex- tra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avi- din-biotin complex using isozyme selective antibod- ies. Results: There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and non- cancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepat- ic cholangiocarcinomas (86%, 48/56) was signifi- cantly higher than their matched tissues (39%, 12/ 31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra- hepatic cholangiocarcinoma was related to the metas- tasis of lymph nodes, distant organs or tissues (P< 0.05) as well as the degree of tumour differentiation (P<0.05). Conclusions: The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.
文摘Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutagens").Control ofproliferation and differentiation within andbetween tissues is mediated by
基金Natural Science Foundation of Fujian Province,China,No.K98036
文摘AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly selected from 10 counties withinFujian Province.All subjects were localresidents who had been living in Fujian Provincefor more than 20 years,within the age group of45-74 years.Trained interviewers conductedface-to-face interviews with a standardizedquestionnaire,which covered the frequency andamount of food intake,dietary habit,tobaccoand alcohol consumption and history of chronicgastric diseases.Univariate and multivariateanalyses were performed using Epi-info and SASstatistical packages,respectively.RESULTS A significant correlation betweenmonthly consumption of fish sauce and mortalityof gastric cancer was found.Pearson’scoefficient of correlation was statisticallysignificant with r=0.7356 for males,r=0.5246for females(P【0.01).In the multivariateanalysis,consumption of fish sauce still showedan association with the risk of gastric cancer.No significant positive correlation betweenesophagus cancer,liver cancer,colon cancerand consumption of fish sauce were observed.CONCLUSION Long-term intake of fish saucemay be related to high mortality of gastriccancer.Consumption of fish sauce might be oneof important and unique etiologic factors ofgastric cancer in Fujian Province.Furtherstudies are needed to confirm this ecologicalstudy.
基金National Natural Science Foundation of China,№48970193
文摘INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver
基金Supported by the Military Science Foundation of China,No.96M060
文摘INTRODUCTIONThe field of gastrointestinal hormones has expanded at a dizzying rate[1-4].Gastrointestinal hormones as regulatory peptides that appear to be major components of bodily integration and have important regulatory actions on physioligical function of the gastrointestinal tract .The successful isolation of some gastrointestinal hormones and the development of sensitive methods for their detection have led to the unexpected finding that they also exist in the brain .
基金supported by a Grant-in Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant No.18406026)by the foundation for Scientific Research and Technology,Health Bureau of Dalian(Grant No. 2007-73)
文摘Objective To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. Methods Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann Whitney nonparametric U-tests and multiple linear regression. Results The concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 gg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 p.g/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (〈500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens. Conclusion Both mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.
文摘Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). Methods Male and female B6C3F1 mice were exposed, through inhalation, intravenous administration and diet, to 0.5 ppm of ozone, 1.0 mg/kg of NNK and 5000 ppm of DBP, individually and in combination for 16 and 32 weeks. Results No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment. Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks. Conclusion Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions, they induce oviductal carcinomas in B6C3F1 mice.
文摘Color is the main attraction of any fabric. No matter how excellent its constitution, if unsuitably colored it is bound to be a failure as a commercial fabric. Manufacture and use of synthetic dyes for fabric dyeing has therefore become a massive industry today. In fact the art of applying color to fabric has been known to mankind since 3500 BC. WH Perkins in 1856 discovered the use of synthetic dyes. Synthetic dyes have provided a wide range of colorfast, bright hues. However their toxic nature has become a cause of grave concern to environmentalists. Use of synthetic dyes has an adverse effect on all forms of life. Presence of sulphur, naphthol, vat dyes, nitrates, acetic acid, soaps, enzymes chromium compounds and heavy metals like copper, arsenic, lead, cad- mium, mercury, nickel, and cobalt and certain auxiliary chemicals all collectively make the textile effluent highly toxic. Other harmful chemicals present in the water may be formaldehyde based dye fixing agents, chlorinated stain removers, hydro carbon based softeners, non bio degradable dyeing chemicals. These organic materials react with many disinfectants especially chlorine and form by products (DBP’S) that are often carcinogenic and therefore undesirable. Many of these show allergic reactions. The colloidal matter present along with colors and oily scum increases the turbidity, gives the water a bad appearance and foul smell and prevents the penetration of sunlight necessary for the process of photosynthesis. This in turn interferes with the Oxygen transfer mechanism at air water interface which in turn interferes with marine life and self purification process of water. This effluent if allowed to flow in the fields’ clogs the pores of the soil resulting in loss of soil productivity. If allowed to flow in drains and rivers it effects the quality of drinking water in hand pumps making it unfit for human consumption. It is important to remove these pollutants from the waste waters before their final disposal.
文摘The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.