MUTAGENICITY AND CARCINOGENICITY OF FISH SAUCE FROM A COUNTY WITH THE HIGH RISK FOR GASTRIC CANCER IN CHINA

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.

Antimutagenicity of Propolis Against Some 0Mutagens in vivo and in vitro

Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. Results The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P<0.05) were obtained in TA98 strain at 2000 and 3000 mg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P<0.05) appeared at 1000, 2000, and 3000 mg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P<0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P<0.05) only at the dose of 135.0 mg/kg b. w. Conclusion The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.

Removal effect on Mesocyclops leukarti and mutagenicity with chlorine dioxide

Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocylops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide prcoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products （DBPs） of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation ofMesocyclops leukorti can be inactivated effectively and safely by chlorine dioxide pre-oxidation.

Comparison of the Mutagenicity of Exhaust Emissions From Motor Vehicles Using Leaded and Unleaded Gasoline as Fuel

While Unleaded gasoline has the advantage of eliminating lead from automobile exhaust, its potential to reduce the exhaust gas and particles, merits further examination. In the present studies,the concentrations of hydrocarbons (HC) and earbon monoxides (CO) in emissions were analyzed on Santana engine Dynamometer under a standard test cycle, and total exhaust particles were collected from engines using leaded and unleaded gasoline. It was found that unleaded gasoline reduced the emissions of CO and HC, and decreased the quantity of vehicle exhaust particulate matters by 60%.With the unlead gasoline, only 23 kinds of organic substances, adsorbed in the particles, were identified by gas chromatography/mass spectrometer (GC/MS) while 32 components were detected using the leaded gasoline. The results of in vitro Salmonella/ microsomal test and micronucleus induction assay in CHL cells indicated that both types of gasoline increased the number of histidine-independent colonies and the frequencies of micronucleus induction; no significant differellce was found in their mutagenicity.

Studies on Mutagenicity and Teratogenicity of Sarafloxacin

Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.

Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of short-term tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P>0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P > 0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1730, 1/20 and 1/15 LD50 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages.The probability of carcinogenicity of Kuianchun is 23.8%(6 = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.

A Study of the Pesticide Fenthion: Toxicity, Mutagenicity, and Influence on Tissue Enzymes

In this paper results of acute toxicitv (oral and dermal), cumulative toxicitv, subchronic toxicitv. and conjunctiva irritation tests are reported. The mutagenic effects of fenthion. using SCE (in vivo) and UDS(in vitro) as indicators, were also tested. Histochemical changes in enzyme activities (including AChE. ATPase. and AK.P) in tissues were observed. The results showed that the acute toxicitv of fenthion belongs to highly toxic category. The highly cumulative effect of fenthion was also observed. The subchronic toxicitv test. however. did not reveal any abnormal effects except the inhibition of ChE activity in plasma. The dose and ChE activity relationship equation was V=0.82.x+4.71. The SCE and UDS tests revealed no mutagenic potential. In histochemical experiments we found that AChE activity in tissues was markediv inhibited. AKP and ATPase activities at the cortex rcnis were increased in the treated rats.(c) 1990 Academic Press. Inc.

TESTING THE MUTAGENICITY OF FIVE PESTICIDES WITH MICRONUCLEUS TECHNIQUE OF TRADESCANTIA PALUDOSA

Applying the micronucleus technique T.adescanlia paludosa, the mutagenicity of five pesticides, Decis, Sumicid, Cypermethrin, Trichlorphon and Diazinon were tested. The testing results showed that 0.64%, 0.32%, 0.16%, 0.08% of Decis, 0.64%, 0.32%, 0. 16%, 0.04% of Trichlorphon and 0.32%, 0.16%, 0.08%, 0.04% of Diazinon all had mutagenicity on Tradescantia paludosa, but Sumicid and Cypermethrin had no such characteristic.

Mutagenicity Study on Ibopamine: A New Heart Failure Antagonist

Ibopamine(Ibo) is a new effective drug against heart failure. This paper reports the results of mutation tests of chromosome aberration of mammalian cell (Chinese hamster lung cell, CHL) in vitro and reversional mutation test of Salmonella typhimurium bacterium (Ames test) of ibopamine . The results of both tests were negative. Ibo did not have mutagenic effect.

Mutagenicity and Induction of Drug-metabolizing Enzyme Activity by LPG Combustion Particulates in Rats

Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase (AHH) and glutathione S-transferase (GST) in rats. The extracts showed mutagenicity for Salmonella typhimurium strain TA98 and its derivatives TA98NR and TA98/1,8-DNP6 with or without S9 mix. The revertants in strains TA98NR and TA98/1,8-DNP6 were less than 40% and 50% of that in strain TA98 without S9 mix, respectively. Positive results were obtained in mouse bone marrow micronucleus assay. Intratracheal instillation of the extracts led to increase in pulmonary (but not hepatic) AHH and GST activities in rats. It was seen that AHH was more sensitive than GST to induction by the extracts

Mutagenicity of Urine From Individuals Exposed to LPG Combustion Products

The mutngenicity of urine from individua1s exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three stralns in the presence of both rat liver S9 and β-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 μl urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the sarne samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contaln mainly arotnatic compounds as glucuronide conugates. our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic poency between the' pure' exposed (non-srnokers') and the ' pure' smokers' (unexpeed) samples was found in all three tester strains. This might mean that the exopure extent Of mutagens/carcinogens in LPG combustion products for exmped individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that sguergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.

Mutagenicity of Wastewater Extracts from Pulp and Paper Industry

Wastewater samples were collected from pulp and paper mill located in Kashipur (India) and were extracted using dichloromethane (DCM), chloroform and hexane solvents (all were HPLC-grade). The extracts were assayed for their mutagenic potential using Ames Salmonella mutagenicity assay. TA98 strain was found to be the most responsive, in terms of induction factor (Mi) and slope (m) of the initial linear dose-response curve as determined by linear regression analysis up to the increasing doses indicating the presence of frame shift mutagens in the test samples. Mutagenicity of different extracts is arranged as follows: dichloromethane extracted water samples > hexane extracted water samples > chloroform extracted water samples. Hexane extract exhibited maximum mutagenic index of 13.0 and induction factor (Mi) 2.48 with TA98. The order of responsiveness based on the mutagenic index and induction factor for the test samples was in the following order: TA98 > TA97a > TA100 > TA102 > TA104. Our findings suggest that TA97a, TA98, TA100, TA102, TA104 were sensitive towards the wastewater extracts and showed considerable mutagenicity.

Mutagenicity and Genotoxicity of Organic Extracts from Finished Water with Different Treatment Process

Purification of surface water is widely practiced with conventional water treatment processes like coagulation-flocculation, sedimentation, filtration,and disinfection. Some reports have specified that conventional wastewater purification processes do not effectively remove many chemical contaminants,

Evaluation of the Mutagenicity Potential of Trace-Rutinosidase Variety of Tartary Buckwheat (Fagopyrum tataricum Gaertn.) Using the Ames Test

To ensure the safety of “Manten-Kirari”, a non-bitter and trace-rutinosidase variety of Tartary buckwheat, we evaluated its mutagenic activity in a bacterial reverse mutagenicity assay, the Ames test. Salmonella typhimurium TA100, TA1535, TA98, TA153, and Escherichia coli WP2 uvrA were employed as test bacteria. The flour of “Manten-Kirari” was dissolved at 12 - 50,000 μg/mL in DMSO and investigated. The number of revertants did not differ compared to the negative control for all concentrations tested, whereas that in the positive control, the number of revertants was increased with or without metabolic activation for each bacterial strain tested. These results suggested that the flour of the Tartary buckwheat “Manten-Kirari” was not genotoxic.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

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.

2D/3D-QSAR comparative study on mutagenicity of nitroaromatics

Nitroaromatics are typical toxic organic pollutants and are ubiquitous in environment with diverse structures. They are widely used in many industries and formed during many natural and anthropogenic processes. Most of these pollutants are potentially carcinogenic and the as-sessment and prediction of the mutagenicity of nitroaromatics are of great interest. In this paper the structure-mutagenicity relationships of 219 nitroaromatics are investigated by molecular or-bital theory based classic structure-activity relationships and comparative molecular field analysis (CoMFA). A comparison is undertaken in respect of the interpretation of mechanism and predic-tive ability for these two categories of QSAR approaches and highly predictive QSAR models have been developed.

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid（DMAV） is a major urinary metabolite of sodium arsenite（i As~Ⅲ） and induces urinary bladder cancers in rats. DMAVand i As~Ⅲare negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAVand i As~Ⅲin rat urinary bladder epithelium and liver using gpt delta F344 rats.Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg/L DMAV, or 87 mg/L i As~Ⅲ（each 50 mg/L As） for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection（gpt assay） and deletion mutations are identified in the red/gam genes by Spi-selection（Spi-assay）. Results of the gpt and Spi-assays showed that DMAVand i As~Ⅲhad no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand i As~Ⅲare not mutagenic in urinary bladder epithelium or liver in rats.

Quantification of Structurally Alert Mutagenic Impurities in Meropenem Trihydrate Drug Substance by Liquid Chromatography with High Resolution Mass Spectrometer (LC-HRMS)

Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.

Disinfection byproducts in chlorinated or brominated swimming pools and spas: Role of brominated DBPs and association with mutagenicity

Although the health benefits of swimming are well-documented, health effects such as asthma and bladder cancer are linked to disinfection by-products(DBPs) in pool water. DBPs are formed from the reaction of disinfectants such as chlorine(Cl) or bromine(Br) with organics in the water. Our previous study(Daiber et al., Environ. Sci. Technol. 50, 6652;2016) found correlations between the concentrations of classes of DBPs and the mutagenic potencies of waters from chlorinated or brominated swimming pools and spas. We extended this study by identifying significantly different concentrations of 21 individual DBPs in brominated or chlorinated pool and spa waters as well as identifying which DBPs and additional DBP classes were most associated with the mutagenicity of these waters. Using data from our previous study, we found that among 21 DBPs analyzed in 21 pool and spa waters, the concentration of bromoacetic acid was significantly higher in Brwaters versus Cl-waters, whereas the concentration of trichloroacetic acid was significantly higher in Cl-waters. Five Br-DBPs(tribromomethane, dibromochloroacetic acid, dibromoacetonitrile, bromoacetic acid, and tribromoacetic acid) had significantly higher concentrations in Br-spa versus Cl-spa waters. Cl-pools had significantly higher concentrations of ClDBPs(trichloroacetaldehyde, trichloromethane, dichloroacetic acid, and chloroacetic acid), whereas Br-pools had significantly higher concentrations of Br-DBPs(tribromomethane, dibromoacetic acid, dibromoacetonitrile, and tribromoacetic acid). The concentrations of the sum of all 4 trihalomethanes, all 11 Br-DBPs, and all 5 nitrogen-containing DBPs were each significantly higher in brominated than in chlorinated pools and spas. The 8 Br-DBPs were the only DBPs whose individual concentrations were significantly correlated with the mutagenic potencies of the pool and spa waters. These results, along with those from our earlier study, highlight the importance of Br-DBPs in the mutagenicity of these recreational waters.

Anti-lipid-oxidation effects and edible safety evaluation of the oil extracted by a supercritical CO_(2) process from coix seed fermented by Monascus purpureus

The physicochemical properties and composition of coix seed oil produced by Monascus purpureus fermentation and supercritical CO_(2)extraction were determined.Anti-lipid-oxidation and edible safety were evaluated using a cholesterol-fish oil model,acute oral toxicity assay,and genetic toxicity assay in vitro and in vivo,respectively.The results show that the extraction oil from fermented coix seed(FCS-O)had good physicochemical quality and abundant active components with physiological function.In particular,γ-tocotrienol,γ-oryzanol,coixenolide and oleic acid concentrations reached 72.83μg/g,745.96μg/g,9.65 mg/g and 316.58 mg/100 g DW,respectively.The FCS-O exhibited higher antioxidant capability in inhibiting lipid oxidation and peroxidation.Compared to the blank control,the concentrations of 7-ketocholestreol and peroxide only were 8.42μg/mL and 16.16 mmol/kg at 168 h of oxidation(P<0.01).In addition,the FCS-O has been confirmed to be a very safe edible oil,with no acute toxicity(LD50>10 g/kg bw,considered actually non-toxic)and no induced mutagenicity,cytotoxicity or genotoxicity.These results serve as a good safety reference for future application of the oil from fermented coix seed.The development and utilization of this kind of oil will be beneficial as a food,food ingredient,nutritional supplement,or natural food antioxidant to promote good health function.