EROD activities of liver in Mugil so-iuy exposed to benzo(a)pyrene,pyrene and their mixture

The effects on hepatic EROD (7-ethoxyresorufin O-deethylase) in Mugil so-iuy exposedto benzo(a)pyrene (BaP), pyrene and their mixtures of equal concentration were investigated, at concentrations of 0.1, 1.0, 5.0, 10.0, 50.0μg/dm3, in experimental condition. Time-effects and dose-response of the biochemical indexs were observed. The results showed that the hepatic EROD activities were induced by the exposure of BaP, pyrene and their mixtures at high concentration. Dose-response connections were that the hepatic EROD activities were elevated with increasing concentration of the pollutants. The combined effect of BaP and pyrene at 1:1 concentration ratio on hepatic EROD activity was antagonism.

Inhibitory Effect of Green Tea Extract on the Carcinogenesis Induced by Asbestos Plus Benzo(a)pyrene in Rat

In this experiment lung carcinoma was induced by crocidolite plus benzo(a)pyrene in rat. From the cancer models, we observcd that the incidcnce (16.0%) of lung carcinomas was lowel, and the survival time (376 days) of the first case of carcinoma and the mean survival time (758 days) of the rats with carcinoma were higher in the group of rats drinking 2% green tea extract for life than in the positive group (without drinking green tea extract). The mortality ratio (0.5047) was smaller in the cxperimental group than in the positive control group, and the survival curve of the experimental group significantly raised up, in comparison with the positive group.

Resveratrol Attenuates Benzo(a)pyrene-Induced Dysfunctions,Oxidative Stress and Apoptosis in Pancreatic Beta-Cells

Background: Diabetes mellitus is one of the major health problems for people all over the world today. According to international diabetes federation reports, diabetes affects 382 million people worldwide. Environmental pollutants have deleterious effects on glucose metabolism and cause insulin resistance. We aimed to investigate the effects of the environmental pollutants benzo(a)pyrene, and the therapeutic potential of resveratrol. Methods: 20 μM of benzo(a)pyrene was administered after 48 h of resveratrol (80 μM) application for 24 h in INS-1 (832/13) insulinoma cells. The cells were treated with 20 μM benzo(a)pyrene for 24 hours after 48 hours initial preconditions with 10 μM resveratrol. Oxidative stress status, insulin secretion and apoptosis were analyzed by molecular techniques. Results: Though resveratrol increased the antioxidant status which was decreased by benzo(a)pyrene, interestingly, it increased the oxidative status. Resveratrol increased benzo(a)pyrene-depleted reduced glutathione levels to the control level. The mRNA expression levels of beta-cell functions associated with genes insulin-1, insulin-2 and sirtuin-1 were upregulated by resveratrol. Resveratrol treatment elevated the insulin concentration of culture medium, and the mRNA expression of forkhead box protein-1 gene. Resveratrol upregulated benzo(a)pyrene-downregulated p53 gene expression. On the other hand, benzo(a)pyrene-downregulated mRNA expression of B-cell lymphoma-2 was induced by resveratrol treatment. Conclusion: The data showed that resveratrol could reverse the oxidative alterations, functional impairments and the carcinogenetic effects of benzo(a)pyrene in pancreas beta-cells.

L－519，A PHENOLIC COMPOUND，INHIBITS METABOLISM OF BENZO（a）PYRENE AND MUTAGENESIS INDUCED BY BENZO（a）PYRENE

L-519 is a Phenolic compound.In this study,L-519 was found to inhibit the mutagenicity of benzo(a) pyrene[B(a)P] in Salmonella Typhimurium TA 97 and TA 100 and inhibit the cytochrome P-450 mediated metabolism of B(a) P.It also inhibited the epidermal ODC activity induced by croton oil.L-519 also decreased the lipid peroxidation induced by FeSO4 and Cysteine in rat liver microsome system. Our results demonstrated that L-519 exhibited anti-mutagenicity,anti-initiation as well as anti-promotion activities.

THE RAPID DETERMINATION FOR BENZO(a)PYRENE WITH SYNCHRONOUS FLUORESCENCE SPECTROSCOPY SCANNING IN DEFINED RANGE OF DUAL—WAVELENGTHS

A rapid method of determination of BaP in various environmental samples,using synchronous fluorescence spectroscopy scanning in defined range of dual-wavelengths(SFDW)is described in this paper.

FLUOROMETRIC METHOD FOR RAPID DETECTION OF DNA DAMAGE IN HUMAN PERIPHERAL LEUKOCYTES INDUCED BY BENZO(A)PYRENE

A preliminary study on application of Pluorometric Analysis ofDNA Unwinding（FADU）to the detection of DNA strand breaksinduced by indirect environmental mutagen benzo（a）pyrene（BaP）was conducted.The results showed that BaP,activated by PCB-in-duced rat liver S9mixture,could result in obvious increase of DNAstrand breaks in human peripheral leukocytes incubated with

Reduced-glutathione concentrations in Boleophthalmus pectinirostris tissues exposed to benzo(a)pyrene

The concentrations of reduced-glutathione ( GSH) in liver and ovary of Boleophthalmus pectinirostris are quantified. The concentrations of GSH in the ovary are much higher than that of GSH in the liver(nearly 3 times of the liver). The study also investigates the changes of GSH contents in the two organs while the fishes were exposed to benzo(a)pyrene(BaP) at concentrations of 0, 0.05, 0.2 and 0.5 mg/L respectively for up to a week. The concentrations of GSH in the liver of BaP-exposed fish increased significantly with dose, whereas the concentrations of GSH in the ovary decreased significantly compared to controls. The results suggested that both the liver and the ovary are the primary organ in BaP metabolism, and that the changes of GSH levels may represent an adaptive response or toxic effect to Bap exposure.

The benzo(a) pyrene-induced mRNA expression of aromatic hydrocarbon receptor and cytochrome P4501A1 genes in rat liver

Objective To study the benzo(a)pyrene(B[a]P)-induced mRNA expression of aromatic hydrocarbon receptor(AHR)and cytochrome P4501A1(CYP1A1)genes in rat liver.Methods Rats were injected intraperitoneally with 5,10 and 15mg/kg of B[a]P.The total RNAs were extracted from rat livers by RNA purification kit,and the mRNA expression of AHR and CYP1A1 genes was determined by reverse transcription polymerase chain reaction(RT-PCR).β-actin was used as the internal control.The mRNA expression of both AHR and CYP1A1 genes was measured at indicated time points(24,48 and 72h)after B[a]P treatment at three different concentrations(5,10 and 15mg/kg).Results The mRNA expression of AHR gene increased in a time-dependent manner at the concentration of 10mg/kg but not at 5 and 15mg/kg of B[a]P.The mRNA expression of CYP1A1 gene differed significantly at 48h and 24h in rat livers treated with 10 and 15mg/kg dosage of B[a]P.The mRNA expression of AHR and CYP1A1 genes increased with B[a]P treatment in a concentration-dependent manner.The time-dependent increase in mRNA expression was shown by AHR but not by CYP1A1 gene with B[a]P(10mg/kg)treatment.Conclusion This study demonstrates that toxic B[a]P increases the mRNA expression of both AHR and CYP1A1 genes in vivo,suggesting that B[a]P may play a role in cancer genesis by this way.

The biological potency of benzapyrene in the humates composition

The aim of the paper was to determine benz(a)-pyrene in the preparations containing humates and study the benz(a)pyrene biological potency for the agricultural plants. The research methodology included the determination of the dependencies in the system “substance concentration (dose)—effect on the plant”. Concentrations of benz(a)pyrene in 12 samples of the humates preparations and fertilizers based on their trademarks “Irkutsk humates”, obtained from brown coal, varied in the range from 0.3 to 50 mcg/kg, which creates no soil contamination in conditions of the use of preparations. Between contents of benz(a)pyrene and humates there is a correlation (rxy = 0.95;α = 0.05). It is ascertained that the effects of stimulation and/or inhibition of the growth and yield of agricultural plants depend on the concentration of benz(a)pyrene and the method of plant processing. Optimal concentrations of benz(a)pyrene were 150-200 ng/dm3 for preplant way of processing of potato tubers, 3-10 ng/dm3—for top dressing (spraying) and 0.1-0.3 ng/dm3—for dressing under the roots (hydroponic). The obtained results allowed us to offer one of the possible mechanisms of biological potency of humates as the plant growth stimulants, and also a way testing of the preparations by screening of their benz(a)pyrene content.

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.

Stabilization of membrane bound ATPases and lipid peroxidation by carotenoids from Chlorococcum humicola in Benzo(a)pyrene induced toxicity

Objective:To identify the alleralinn of the membrane polenlial and llie effect of carolenoid extracts from Chlorococcum hnmicola(C.humicola) on membrane hound ATPases and lipid peroxidation.Methods:The lolal carotenoids were extracted from C.humicola.Four groups of Swiss albino mice were treated as control,Benzo(a)pyrene[B(a)P],total carotenoids,B(a)P+ total caralenoids respectively for a period of 60 days.Membrane lipid peroxidation and ATPases(Total ATPases,Ca^(2+)-ATPases.Mg^(2+)-ATPases.Na^+K^+- ATPasei were determined in lung,liver and erythrocyte samples.Results:The activity of lolal ATPase was found to be significantly increased in the B(a)P treated liver and lung tissue.Erythrocyte membrane also showed higher ATPase activity which was significantly reverted on total carolenoid treatment.Conclusions: It can be concluded that the changes in membrane potential favour the functional deterioration of physiological system.The overall findings demonstrates that the animals post treated with carolenoid extract from C.humicola may maintains the alterations in membrane bound ATPase and lipid peroxidation in tissues against the carcinogenic chemical and hence aid in establishing the membrane potential action.Then-fore C.humicola can be further extended to exploits its possible application for various health benefits as neulraceulicals and food additives.

Exposure of benzo[a]pyrene induces HCC exosome-circular RNA to activate lung fibroblasts and trigger organotropic metastasis

Background:Benzo[a]pyrene(B[a]P),a carcinogen pollutant produced by combustion processes,is present in the western diet with grilled meats.Chronic exposure of B[a]P in hepatocellular carcinoma(HCC)cells promotes metastasis rather than primary proliferation,implying an unknown mechanism of B[a]P-induced malignancy.Given that exosomes carry bioactive molecules to distant sites,we investigated whether and how exosomes mediate cancer-stroma communications for a toxicologically associated microenvironment.Method:Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells(7404-100Bap Exo)at an environmental relevant dose(100 nmol/L).Lung preeducation animal model was prepared via injection of exosomes and cytokines.The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array.HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis.Profile of B[a]P-exposed exosomes were determined by ceRNA microarray.Interactions between circular RNA(circRNA)and microRNAs(miRNAs)were detected using RNA pull-down in target lung fibroblasts.Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the“on-off”interaction of circRNA-miRNA pairs.We further developed an adenoassociated virus inhalation model to examine mRNA expression specific in lung,thereby exploring the mRNA targets of B[a]P induced circRNA-miRNA cascade.Results:Lung fibroblasts exert activation phenotypes,including focal adhesion and motility were altered by 7404-100Bap Exo.In the exosome-educated in vivo model,fibrosis factors and pro-inflammatory molecules of are up-regulated when injected with exosomes.Compared to non-exposed 7404 cells,circ_0011496 was up-regulated following B[a]P treatment and wasmainly packaged into 7404-100Bap Exo.Exosomal circ_0011496 were delivered and competitively bound to miR-486-5p in recipient fibroblasts.The down-regulation of miR-486-5p converted fibroblast to cancer-associated fibroblast via regulating the downstream of Twinfilin-1(TWF1)and matrix metalloproteinase-9(MMP9)cascade.Additionally,increased TWF1,specifically in exosomal circ_0011496 educated lungs,could promote cancer-stroma crosstalk via activating vascular endothelial growth factor(VEGF).These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion,as a consequence of a pre-metastatic niche formation.Conclusion:We demonstrated that B[a]P-induced tumor exosomes can deliver circ_0011496 to activate miR-486-5p/TWF1/MMP9 cascade in the lung fibroblasts,generating a feedback loop that promoted HCC metastasis.

Exposure to polycyclic aromatic hydrocarbons with special focus on cancer

Polycyclie aromatic hydrocarbons(PAHs) are a group of compounds consisting of two or more fused aromatic rings.Most of them are formed during incomplete combustion of organic materials such as wood and fossil fuels,petroleum products,and coal.The composition of PAH mixtures varies with the source and is also affected by selective weathering effects in the environment.PAHs are ubiquitous pollutants frequently found in a variety of environments such as fresh water and marine sediments,the atmosphere,and ice.Due to their widespread distribution,the environmental pollution due to PAHs has aroused global concern.Many PAHs and their epoxides are highly toxic,mutagenic and/or carcinogenic to microorganisms as well as to higher forms of life including humans.The main aim of this review is to provide contemporary information on PAH sources,route of exposure,worldwide emission rate,and adverse effects on humans,especially with reference to cancer.

Evaluation of antigenotoxic effects of carotenoids from green algae Chlorococcum humicola using human lymphocytes

Objective:To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes.Methods:Organic,solvent extracts of Chlorococcum humicola(C.humicola)were used for the phytochemical analysis.The available carotenoids were assessed by HPLC,and LC-MS analysis.The genotoxicity was induced by the benzo(a)pyrene in the lymphocyte culture,the genotoxic and antigenotoxic effects of algal carotenoids with and without genotoxic inducer were evaluated by chromosomal aberration(CA),sister chromatid exchange(SCE)and micronucleus assay(MN).Results:The results of the analysis showed that the algae were rich in carotenoids and fatty acids.In the total carotenoids lutein,β-carotene andα-carotene were found to be present in higher concentration.The frequency of CA and SCE increased by benzo(a)pyrene were significantly decreased by the carotenoids(P<0.05 for CA,P<0.001 for SCE).The MN frequencies of the cells were significantly decreased by the treatment with carotenoids when compared with the positive controls(P<0.05).Conclusions:The findings of the present study demonstrate that,the green algae C.humicola is a rich source of bioactive compounds especially carotenoids which effectively fight against environmental genotoxic agents,the carotenoids itself is not a genotoxic substance and should be further considered for its beneficial effects.

Approaches to municipal wastewater irrigation and environmental protection

To reuse the water and nutrient resources from ecological point of view the goals, criteria and constraint conditions of the scientifically municipal wastewater irrigation are discussed as well as the practice in major municipal wastewater irrigation areas in China is introduced, of which particularly the effects of municipal water irrigation mixing with oil refinery wastewater on the agricultural ecosystem are studied and described. It has been revealed that benzo(a)pyrene in various parts of paddy crop is attributed to air pollution, water-soil pollution and biosynthesis of plant. Of exogenous contributions of benzo(a)pyrene in paddy shoot system under natural condition, the dominant factor is the air pollution, whereas the water-soil factor is considered to be secondary. Therefore, it is mostly urgent to control the air pollution source of benzo(a)pyrene, to which the edible parts of various green plants are exposed directly.

Adsorption and partition of benzo(a)pyrene on sediments with different particle sizes from the Yellow River

Experiments have been carried out to study the sorption of Benzo(a)pyrene(Bap)on sediment particles from the Yellow River using a batch equilibration technique.Effects of particle size on the adsorption and partition of Bap were investigated with the particle content of 3 g/L.Several significant results were obtained from the study.(1)Isotherms of Bap could be fitted with the dual adsorption-partition model under different particle sizes,and the measured value of the adsorption and partition was in agreement with the theoretical value of the dual adsorption-partition model.(2)When the particle diameter was d i 0.025 mm,the adsorp-tion was predominant in the sorption of Bap,which accounted for 68.7%-82.4%of the sorption.For the particles with the size of 0.007 mm≤d<0.025 mm,the adsorption was predominant when the equilibrium concentration of Bap was 0-8.87 mg/L in the water phase;and the partition was pre-dominant when the equilibrium concentration of Bap was higher than 8.87 mg/L in the water phase.When the particle diameter was d<0.007 mm,the partition was predominant.(3)On the point of particle size,the contribution of adsorption to sorption followed the order:“d≥0.025 mm”>“0.007 mm ≤d<0.025 mm”>“d<0.007 mm”.(4)The partition coeffi-cients of Bap in solids with different particle sizes were linearly correlated with the organic content,and the Koc of Bap was about 1.26 × 10^(5)(L/kg).

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%–18.5%of hospitalized adults,calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection.Here,we show that cigarette smoke extract(CSE)and carcinogen benzo(a)pyrene(BaP)increase ACE2 mRNA but trigger ACE2 protein catabolism.BaP induces an aryl hydrocarbon receptor(AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination.ACE2 in lung tissues of non-smokers is higher than in smokers,consistent with the findings that tobacco carcinogens downregulate ACE2 in mice.Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells.Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein,tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide(anti-BPDE)is a metabolite of benzo[a]pyrene(B[a]P)and acts as a potent mutagen in mammalian systems.However,molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood.Here,we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells(16HBE-T)transformed by exposure to anti-BPDE.The levels of mRNA and pro-tein of c-Myc were examined in the 16HBE-T and vehicle-treated control cells(16HBE-N)by using different meth-ods respectively,including reverse transcriptase-polymer-ase chain reaction(RT-PCR),quantitative real-time PCR(Q-PCR),western blot and immunocytochemical meth-ods.The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T,as compared with those of the 16HBE-N.Likewise,the expression of c-Myc protein was significantly enhanced as compared with those of the control cells.Moreover,the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T.In conclu-sion,the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells,which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.