Cis-bifenthrin inhibits cortisol and aldosterone biosynthesis in human adrenocortical H295R cells via cAMP signaling cascade.

Cis-bifenthrin (cis-BF) is a common-used pyrethroid insecticide frequently detected in environmental and biological matrices. Mounting evidence highlights the endocrine disrupting effects of cis-BF due to anti-estrogenic or anti-androgenic activity. However, little is known about the exposure effects of cis-BF on adrenal cortex function. In this study, effects of cis-BF on biosynthesis of adrenal steroids, as well as the potential mechanisms were investigated in human adrenocortical carcinoma (H295R) cells. Cis-BF decreased basal production levels of cortisol and aldosterone, as well as cAMP-induced production of cortisol. Both he basal and cAMP-stimulated transcriptional levels of several steroidogenic genes were significantly down-regulated by cis-BF. As an important rate-limiting enzyme in steroidogenesis, the protein level of StAR was prohibited by cis-BF on both basal and cAMP-induced conditions. Intracellular level of cAMP was significantly reduced by cis-BF. Overall, these data suggest that cis-BF may inhibit the biosynthesis of cortisol and aldosterone via disrupting cAMP signaling cascade.

A comparison of removal efficiencies of conventional drinking water treatment and advanced treatment equipped with ozone-biological activated carbon process.

ABSTRACTUsing raw water from a shallow water supply reservoir located in the lower Yangtze River region, the removal efficiencies of conventional treatment on dissolved organic matter (DOM) and disinfection by-products formation potential (DBPFP) were compared with an advanced treatment that equipped with ozone-biological activated carbon (O3-BAC) process. The results showed that the advanced treatment was more efficient than the conventional treatment at removing dissolved organic carbon (DOC; 40-67% removal), UV254 (61-81% removal), the trihalomethane formation potential (THMFP; 37-70% removal) and the haloacetic acid formation potential (HAAFP; 35-89% removal). The sand filter in the conventional treatment process was identified as the main contributor to decreasing DOC, UV254 and DBPFP. The O3-BAC in advanced treatment was found to decrease THMFP and HAAFP, with removal rates of 17-40% and 22-59%, respectively. To improve the water quality of effluents, advanced treatment with O3-BAC should be used to treat raw water from the shallow water supply reservoir in lower Yangtze River. However, the increased DBPFP yield, which is proportional to the potential health risks, should not be ignored.

Elevated tissue Cr levels, increased plasma oxidative markers, and global hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium dichromate in drinking water.

Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.

Transgenerational impaired male fertility with an Igf2 epigenetic defect in the rat are induced by the endocrine disruptor p,p'-DDE.

STUDY QUESTION: What are the epigenetic mechanisms underlying the transgenerational effect of p,p'-DDE on male fertility? SUMMARY ANSWER: Impaired male fertility with an Igf2 epigenetic defect is transgenerationally inherited upon exposure of p,p'-DDE. WHAT IS KNOWN ALREADY: p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is one of the primary metabolite products of the ancestral organochlorine pesticide dichlorodiphenoxytrichloroethane. As it is a known anti-androgen endocrine disruptor, it could cause harmful effects on the male reproductive system. STUDY DESIGN, SIZE, DURATION: Pregnant rats (F0) were administered with p,p'-DDE or corn oil at the critical time of testis development, i.e. from gestation days 8 to 15. Male and female rats of the F1 generation were mated with each other to produce F2 progeny. To reveal whether the transgenerational phenotype is produced by the maternal or paternal line, F3 progeny were generated by intercrossing control (C) and treated (DDE) males and females of the F2 generation according to the following groups: (i) C♂-C♀, (ii) DDE♂-DDE♀, (iii) DDE♂-C♀ and (iv) C♂-DDE♀. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mature sperm and testes were collected from male offspring of the F1-F3 generations for the examination of male fertility parameters, i.e. sperm count and motility, testis histology and apoptosis. Expression of the imprinted genes, H19 and Igf2, was detected by real-time PCR. Igf2 DMR2 methylation was analyzed by bisulfite genomic sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: Upon exposure of p,p'-DDE, the male F1 generation showed impaired male fertility and altered imprinted gene expression caused by Igf2 DMR2 hypomethylation. These defects were transferred to the F3 generation through the male germline. LIMITATIONS, REASONS FOR CAUTION: This study has examined the effect of p,p'-DDE only on the sperm number and motility and the possible mechanism of Igf2 DMR2 methylation in vivo and thus has some limitations. Further investigation is necessary to focus on the epigenetic effects of p,p'-DDE at the genome level and to include a more detailed semen quality analysis including sperm morphology assessment. WIDER IMPLICATIONS OF THE FINDINGS: Impaired male fertility with epigenetic alterations is transgenerationally inherited after environmental exposure of p,p'-DDE, posing significant implications in the etiology of male infertility. STUDY FUNDING/COMPETING INTERESTS: The present research was supported by National Natural Science Fund for Young Scholar (81102161), the Natural Science Fund of Zhejiang Province (LY14H260004) and funding from the Health Department of Zhejiang Province (201475777). No competing interests are declared.

Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.

Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5-15 µM potassium dichromate or 1.25-5 µg/cm² lead chromate for 2-24 hours. Cell cycle was arrested at G1 phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV)-induced G1 phase arrest, but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).

DNA damage and oxidative stress in human B lymphoblastoid cells after combined exposure to hexavalent chromium and nickel compounds.

In the present study, human B lymphoblastoid cells were exposed to potassium dichromate and/or nickel chloride for 24h or 48h. The cell viability and DNA damage induced by these compounds was measured with the CCK-8 assay and Comet assay, respectively. In addition, the generation of reactive oxygen species (ROS) and the levels of malondialdehyde (MDA) were measured using commercially available kits. Our results indicated that potassium dichromate could decrease cell viability and induce DNA damage in human B lymphoblastoid cells in a time - and concentration - dependent manner, but the toxicity of nickel chloride was not so obvious at concentrations used in our study. The results of ROS showed that both two compounds could only induce weak elevation of ROS level, but MDA levels were significantly enhanced. Antagonistic effects of cytotoxicity were mainly found between Cr (VI) and Ni (II), and synergistic effects of DNA damage and oxidative stress were partially found between these two compounds. Moreover, there were good correlations between the results of comet assay and the results of oxidative stress assays. It is suggested that synergistic DNA damage induced by simultaneously exposure of hexavalent chromium and nickel compounds is possibly related to oxidative stress.

Chemokine (C-C motif) ligand 22 is down-regulated in a human B lymphoblastoid cell line by PCB153 and in residents from PCBs-contaminated areas.

Polychlorinated biphenyls (PCBs) are ubiquitous, persistent pollutants found in the environment and human tissues. Exposure to PCBs is of great concern to human health because they are known to cause neurological, reproductive, endocrinal, and other effects. The aim of the present study was to find some novel gene markers induced by PCBs through a combination of microarray screening followed by validating with quantitative real time PCR in vitro and in population investigation. In the present study, gene expression profiles of human B lymphoblastoid cells treated with different concentrations of non-coplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) were analyzed using microarray. The differentially expressed genes were further confirmed by real-time PCR in vitro and in individuals from PCBs-contaminated sites. Our results indicated an overlap of 15 differentially expressed genes among samples treated with different concentrations of PCB153, and six of them were selected for validating with qRT-PCR. Two up-regulated genes (CCDC92 and TMEM175) and three down-regulated genes (CCL22, GZMK, and STK38L) were further confirmed by qRT-PCR in vitro. The expression levels of CCL22 in individuals from PCBs-contaminated sites were significantly (P<0.05) lower than those in controls. Therefore, CCL22 seems to be a sensitive gene marker induced by PCBs, although it needs to be confirmed by further studies with a larger number of subjects.

Thyroid endocrine dysregulation and erythrocyte DNA damage associated with PBDE exposure in juvenile crucian carp collected from an e-waste dismantling site in Zhejiang Province, China.

In the present study, 40 juvenile crucian carp (Carassius auratus) were caught from a river close to an electronic waste (e-waste) site (exposed group) and another located 80 km away from the e-waste site (control group) in Zhejiang, China. Results indicated that muscle levels of polybrominated diphenyl ethers (median PBDEs, 235.98 ng/g wet wt; range, 7.70-703.31 ng/g wet wt), serum levels of thyroid-stimulating hormone (median TSH, 2.32 µIU/ml; range, 2.05-2.72 µIU/ml) and erythrocyte DNA damage level (median Olive tail movement, 16.27 µm; range, 4.28-27.51 µm) were higher in the exposed group than those in the control group (0.56 ng/g wet wt, range, 0.34-1.24 ng/g wet wt, p < 0.01; 1.70 µIU/ml, range, 1.40-2.08 µIU/ ml, p < 0.01; 6.06 µm, range, 2.01-10.72 µm, p < 0.01, respectively). Thyroxine (T4) was significantly lower in the exposed group (8.97 µIU/ml) than in the control group (12.47 µIU/ml). In addition, thyroid endocrine disorder and erythrocyte DNA damage levels were significantly associated with polybrominated diphenyl ether exposure. Hence, PBDEs may affect wild fish populations in real ecosystems with thyroid endocrine disruption and DNA damage.

[Male reproductive toxicity of polychlorinated biphenyls].

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants with estrogen-like effects that exist widely in the environment, and its male reproductive toxicity is arousing more and more attention. Studies indicate that different types of cells in the testis respond differently to PCBs exposure. This article presents an overview on the toxicity of PCBs to testicular germ cells, Leydig cells, Sertoli cells and male offspring. We suggest that deeper studies focus on the mechanism of PCBs according to the results of investigations on male reproductive epidemiology. An insight into the intercellular junctions of Sertoli cells might produce a breakthrough in the studies of the testicular toxicity of PCBs.

Levels of PCDD/Fs and DL-PCBs in selected foods and estimated dietary intake for the local residents of Luqiao and Yuhang in Zhejiang, China.

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were measured by high resolution gas chromatograph/high resolution mass spectrometer (HRGC/HRMS) in six food groups from Luqiao (LQ) where the e-waste has been recycled and from Yuhang (YH) where the agriculture dominates in Zhejiang Province in China. The total WHO-TEQ values of PCDD/Fs and DL-PCBs in selected foods from LQ were significantly much higher than those from YH. The highest level of the total WHO-TEQ was in crucian carp (10.87 pg g(-1) w.w.) followed by duck (3.77 pg g(-1) w.w.), hen eggs (2.80 pg g(-1) w.w.), chicken (2.43 pg g(-1) w.w.), rice (0.08 pg g(-1) w.w.) and vegetables (0.022 pg g(-1) w.w.) in LQ. By contrast, the highest levels were measured in duck (0.74 pg g(-1) w.w.) followed by hen eggs (0.69 pg g(-1) w.w.), crucian carp (0.55 pg g(-1) w.w.), chicken (0.44 pg g(-1) w.w.), vegetables (0.002 pg g(-1) w.w.) and rice (0.0002 pg g(-1) w.w.) in YH, respectively. The monthly intake of PCDD/Fs and DL-PCBs for the local residents was 401.75 pg WHO-TEQ g(-1) w.w. in LQ, which is above the provisional tolerable monthly intake (PTMI) set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). We determined a monthly intake of 37.13 pg WHO-TEQ g(-1)w.w. in YH, which is below the PTMI. Crucian carp was the predominant contributor to the estimated monthly intake (EMI), accounting for 67.74% and 36.51% in LQ and YH, respectively. High levels of PCDD/Fs and DL-PCBs in selected foods indicate severe contamination of these pollutants in the e-waste recycling site.

[PCBs concentrations in human milk collected from a polluted area--exposure risk for feeding infants].

OBJECTIVE: To determine the concentration of PCBs and the distribution of dioxin-like compounds in human milk collected from a polluted area where discarded electronic equipment is dismantled, and to evaluate the risk for feeding infants. METHODS: The authors collected 20 and 12 milk samples from the polluted area and nearby town, respectively. Milk samples were analyzed for total PCBs (t-PCBs) by gas chromatography, and two mixed milk samples from the two areas were detected the distribution of dioxin-like compounds. RESULTS: t-PCBs in human milks of polluted area and control area were 0.39 - 3.92 microg/g fat and 0.46 microg/g (only one sample was detectable), respectively. The TEQ of PCB126 contribute to total TEQ of dioxin-like compounds was similar to other countries and regions. The TEQs of PCBs of the polluted and control area were 59 pg/g fat and 6 pg/g fat, respectively. CONCLUSION: The TEQ of PCBs of polluted area was much higher than other countries and regions, and the dioxin-like compounds intake of infants was much higher than the Tolerable Daily Intake (TDI) for dioxin recommended by WHO.