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Estrogens and estrogen mimics are aquatic contaminants that can elicit a variety of deleterious effects in exposed fauna. One of the most potent xenoestrogens found in the aquatic environment is 17α-ethinylestradiol (EE(2)), the pharmaceutically derived semi-synthetic hormone found in oral contraceptives and hormone replacement therapies. Exposure to 100 ng/L EE(2) has previously been shown to profoundly decrease functional hepatic nucleotide excision repair (NER) processes in adult zebrafish in correlation with dramatic decreases in the abundance of hepatic XPC and XPA transcripts; however, its effects on these processes in embryos are currently unknown. Because developing organisms are known to have increased sensitivities to endocrine disrupting compounds such as EE(2), the goal of this study was to examine the impacts of estrogen exposure on mRNA expression of these two key NER genes in zebrafish embryos during the first 4 days of development. Embryos were exposed from 0 h post fertilization (hpf) to waterborne EE(2), its major metabolite, estrone (E(1)), or combinations of the two compounds and sampled at 12, 24, 48, 72 and 96 hpf. Increased abundance of vitellogenin-1 (VTG1) mRNA, a bioindicator of estrogen exposure, was evident as early as 24 hpf in embryos that were co-exposed to EE(2) and E(1) and this effect was sustained throughout 96 hpf. Embryos exposed to EE(2) alone exhibited elevated VTG1 beginning at 72 hpf. In contrast to observations from adult zebrafish exposed to EE(2), embryos did not show any change in mRNA abundance of the excision repair gene, XPC, during the first 4 days of development. However, co-exposure to EE(2) and E(1) elicited an increase in XPA mRNA abundance at 48 and 72 hpf, which was the opposite response as that observed in exposed adults where hepatic XPA mRNA abundance decreased after EE(2) exposure. These differences between embryos and adults suggest that alteration of NER gene transcription by EE(2) is operating under different stimuli during development., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The environmental pollutants inorganic arsenic (iAs) and benzo[a]pyrene (B[a]P) are carcinogens often found together in groundwater. The hepatic metabolism of B[a]P is a multi-step process requiring several Phase I and Phase II enzymes, notably cytochrome p450 1A (CYP1A), epoxide hydrolase (EH), and glutathione S-transferase (GST). The purpose of this study was to examine the effect of arsenite (As(III)) on the activity of these enzymes in vivo utilizing adult zebrafish (Danio rerio). Zebrafish were exposed to either 0.4 microM B[a]P, 0.4 microM B[a]P+0.4 microM As(III), 0.4 microM B[a]P+8 microM As(III), 0.4 microM As(III), or 8 microM As(III) for 7 days. Co-exposures to As(III) and B[a]P led to significant decreases in CYP1A enzyme activity (approximately 3-fold) when compared to exposure to B[a]P alone. No similar effects occurred with EH or GST, although B[a]P exposure did significantly increase EH activity. Furthermore As(III) and B[a]P co-exposures significantly decreased CYP1A transcript levels (up to 35-fold) when compared to B[a]P. However, B[a]P-induced CYP1A protein levels remained elevated following co-exposures to As(III). This evidence suggests that As(III) has the potential to modify components of the B[a]P biotransformation pathway in vivo via a disruption of CYP1A activity by way of both pre- and post-translational mechanisms., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Wastewater treatment effluent is a complex mixture of anthropogenic pollutants including estrogenic substances and chemicals, such as polyaromatic hydrocarbons, that cause bulky DNA adducts. Significant research focuses on reproductive effects of aquatic estrogens from wastewater treatment plants. However, other studies suggest genotoxic and immunological effects occur at lower concentrations of wastewater treatment effluent than reproductive endpoints. Recently, effects of estrogen on DNA repair processes in zebrafish have been suggested as a possible mechanism by which estrogen can modulate incidence of DNA mutations. Because wastewater treatment facilities are a significant source of estrogenic compounds, we hypothesized that exposure to whole effluents would also affect DNA repair in zebrafish (Danio rerio). Exposure to effluent from multiple treatment facilities in northern Maine decreased repair of DNA adducts in zebrafish liver cells. Expression of two nucleotide excision repair genes, XPC and XPA, were quantified and showed varied response after exposure in adult male zebrafish. Evidence of estrogen and aryl hydrocarbon receptor activation after exposure varied between treatment plants and temporally within treatment plants when evaluated using a traditional biomarker, vitellogenin-1 (VTG) and, cytochrome p450 1A1 (CYP1A1) mRNA abundance. This research highlights the continuing importance of examining non-reproductive effects of wastewater treatment effluent.

Juvenile rainbow trout (Oncorhynchus mykiss) were subjected to a 2-day radioactive pulse of 110mAg at 11.9 microg/l (as AgNO3), followed by a 19-day post-tracer exposure to non-radioactive Ag(I) (3.8 microg/l). The distribution of 110mAg in the gills, liver, intestine, kidney, brain and remaining carcass was investigated over a 19-day post-tracer period. Initially, the intestine contained the highest proportion of the 110mAg burden (34%), however, by day 8, less than 5% of the total radioactivity remained in this tissue. The majority of the 110mAg eliminated from the intestine appeared to distribute to the liver. Eventually, the 110mAg content in the liver accounted for as much as 65% of the total radioactivity in the fish. Apart from the liver and intestine, only the gills and carcass contained any appreciable amount (>5%) of the total body 110mAg content. Liver and gill samples were fractionated using differential centrifugation techniques to discern the subcellular distribution of 110mAg in these tissues. In the liver, the 110mAg levels in the cytosolic fraction increased from 35% to 72% of the total cellular burden between days 8 and 19, respectively. The radioactive pulse in the gills was predominantly found in a membrane compartment termed the nuclear fraction ( approximately 60% of the total). Little change was observed over time (day 8 to day 19) to the subcellular distribution of Ag in the gills. Using size-exclusion chromatography, most ( approximately 70%) of the 110mAg content in the liver cytosol eluted at a molecular weight characteristic of metallothionein. The cytosolic distribution of 110mAg in gills was quite diffuse, occurring primarily in the heavy molecular weight fractions.