@article{casabar_das_dekrey_gardiner_cao_rose_wallace_2010, title={Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor}, volume={245}, number={3}, journal={Toxicology and Applied Pharmacology}, author={Casabar, R. C. T. and Das, P. C. and DeKrey, G. K. and Gardiner, C. S. and Cao, Y. and Rose, R. L. and Wallace, A. D.}, year={2010}, pages={335–343} } @article{hannas_das_li_leblanc_2010, title={Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna}, volume={5}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0012453}, DOI={10.1371/journal.pone.0012453}, abstractNote={Background Nitrate and nitrite (jointly referred to herein as NOx) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NOx undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes. Methodology/Principal Findings These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO3 −) and nitrite (NO2 −) to nitric oxide using amperometric real-time nitric oxide detection. Both NO3 − and NO2 − were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO2 − to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO3 − and NO2 −. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers. Conclusions/Significance Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.}, number={8}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Hannas, Bethany R. and Das, Parikshit C. and Li, Hong and LeBlanc, Gerald A.}, editor={Pan, XiaopingEditor}, year={2010}, month={Aug}, pages={e12453} } @misc{cooper_laws_das_narotsky_goldman_tyrey_stoker_2007, title={Atrazine and reproductive function: Mode and mechanism of action studies}, volume={80}, number={2}, journal={Birth Defects Research. Part B, Developmental and Reproductive Toxicology}, author={Cooper, R. L. and Laws, S. C. and Das, P. C. and Narotsky, M. G. and Goldman, J. M. and Tyrey, E. L. and Stoker, T. E.}, year={2007}, pages={98–112} } @article{das_cao_cherrington_hodgson_rose_2006, title={Fipronil induces CYP isoforms and cytotoxicity in human hepatocytes}, volume={164}, ISSN={["1872-7786"]}, DOI={10.1016/j.cbi.2006.09.013}, abstractNote={Recent studies have demonstrated the potential of pesticides to either inhibit or induce xenobiotic metabolizing enzymes in humans. Exposure of human hepatocytes to doses of fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazole-3-carbonitrile) ranging from 0.1 to 25 μM resulted in a dose dependent increase in CYP1A1 mRNA expression (3.5 to ∼55-fold) as measured by the branched DNA assay. In a similar manner, CYP3A4 mRNA expression was also induced (10–30-fold), although at the higher doses induction returned to near control levels. CYP2B6 and 3A5 were also induced by fipronil, although at lower levels (2–3-fold). Confirmation of bDNA results were sought through western blotting and/or enzyme activity assays. Western blots using CYP3A4 antibody demonstrated a dose responsive increase from 0.5 to 1 μM followed by decreasing responses at higher concentrations. Similar increases and decreases were observed in CYP3A4-specific activity levels as measured using 6β-hydroxytestosterone formation following incubation with testosterone. Likewise, activity levels for a CYP1A1-specific substrate, luciferin CEE, demonstrated that CYP1A1 enzyme activities were maximally induced by 1 μM fipronil followed by dramatically declining activity measurements at 10 and 25 μM. Cytotoxic effects of fipronil and fipronil sulfone were examined using the adenylate kinase and the trypan blue exclusion assays in HepG2 cells and human hepatocytes. The results indicate both that HepG2 cells and primary human hepatocytes are sensitive to the cytotoxic effects of fipronil. The maximum induction of adenylate kinase was ca. 3-fold greater than the respective controls in HepG2 and 6–10-fold in the case of primary hepatocytes. A significant time- and dose-dependent induction of adenylate kinase activity in HepG2 cells was noted from 0.1 to 12.5 μM fipronil followed by decreasing activities at 25 and 50 μM. For fipronil sulfone, cytotoxic effects increased throughout the dose range. The trypan blue assay indicated that cytotoxic effects contributing to an increase of greater than 10% of control values was indicated at doses above 12.5 μM. However, fipronil sulfone induced cytotoxic effects at lower doses. The possibility that cytotoxic effects were due to apoptosis was indicated by significant time- and dose-dependent induction of caspase-3/7 activity in both HepG2 cells and human hepatocytes. Fipronil mediated activation of caspase-3/7 in concurrence with compromised ATP production and viability are attributed to apoptotic cell death.}, number={3}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Das, Parikshit C. and Cao, Yan and Cherrington, Nathan and Hodgson, Ernest and Rose, Randy L.}, year={2006}, month={Dec}, pages={200–214} }