@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{wallace_cao_chandramouleeswaran_cidlowski_2010, title={Lysine 419 targets human glucocorticoid receptor for proteasomal degradation}, volume={75}, number={12}, journal={Steroids}, author={Wallace, A. D. and Cao, Y. and Chandramouleeswaran, S. and Cidlowski, J. A.}, year={2010}, pages={1016–1023} }
 @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} }
 @article{cao_lu_long_hong_sheng_2005, title={Development of an ELISA for the detection of bromoxynil in water}, volume={31}, ISSN={["1873-6750"]}, DOI={10.1016/j.envint.2004.06.002}, abstractNote={For development of an indirect competitive enzyme-linked immunosorbent assay (ELISA) for the nitrile herbicide bromoxynil, the polyclonal antibodies raised against 2,6-dibromo-4-cyano-phenoxyacetic acid (hapten) conjugated to bovine serum albumin (BSA) by the N-hydroxysuccinimide-activated ester method. Antiserum with a sufficiently high titer to provide the determinations of targeted compounds was obtained only 77 days after the primary immunization. Antiserum A2 was applied to the residual analysis of some water samples, under optimized ELISA condition, the quantitative working range was from 10 to 500 ppb with a limit of detection of 5 ppb. Cross-reactivity to structurally similar agrochemicals and related chemicals was determined. The antiserum showed little cross-reactivity with 2,6-dibromophenol and bromoxynil octanoate ester which have a dibromophenol group as common structure, but showed no cross-reactivity with other herbicides. Each water sample (river water, tap water, purified water, and bottled water) had a matrix effect and was investigated by adding Tween20 in the assay buffer. These four kinds of water samples were fortified with bromoxynil at several concentration levels and were directly analyzed with only dilution with an equal volume of antiserum solution, the mean recovery was 102.3%, and the mean coefficient of variation was 5.96%. The proposed ELISA turned out to be a powerful tool for monitoring of residual bromoxynil in water samples at trace level.}, number={1}, journal={ENVIRONMENT INTERNATIONAL}, author={Cao, YS and Lu, YT and Long, SY and Hong, JB and Sheng, GQ}, year={2005}, month={Jan}, pages={33–42} }
 @article{rose_tang_choi_cao_usmani_cherrington_hodgson_2005, title={Pesticide metabolism in humans, including polymorphisms}, volume={31}, journal={Scandinavian Journal of Work, Environment & Health}, author={Rose, R. L. and Tang, J. and Choi, J. and Cao, Y. and Usmani, A. and Cherrington, N. and Hodgson, E.}, year={2005}, pages={156–163} }
 @article{tang_cao_rose_hodgson_2002, title={In vitro metabolism of carbaryl by human cytochrome P450 and its inhibition by chlorpyrifos}, volume={141}, ISSN={["0009-2797"]}, DOI={10.1016/S0009-2797(02)00074-1}, abstractNote={Carbaryl is a widely used anticholinesterase carbamate insecticide. Although previous studies have demonstrated that carbaryl can be metabolized by cytochrome P450 (CYP), the identification and characterization of CYP isoforms involved in metabolism have not been described either in humans or in experimental animals. The in vitro metabolic activities of human liver microsomes (HLM) and human cytochrome P450 (CYP) isoforms toward carbaryl were investigated in this study. The three major metabolites, i.e. 5-hydroxycarbaryl, 4-hydroxycarbaryl and carbaryl methylol, were identified after incubation of carbaryl with HLM or individual CYP isoforms and analysis by HPLC. Most of the 16 human CYP isoforms studied showed some metabolic activity toward carbaryl. CYP1A1 and 1A2 had the greatest ability to form 5-hydroxycarbaryl, while CYP3A4 and CYP1A1 were the most active in generation of 4-hydroxycarbaryl. The production of carbaryl methylol was primarily the result of metabolism by CYP2B6. Differential activities toward carbaryl were observed among five selected individual HLM samples with the largest difference occurring in the production of carbaryl methylol. Co-incubations of carbaryl and chlorpyrifos in HLM greatly inhibited carbaryl metabolism. The ability of HLM to metabolize carbaryl was also reduced by pre-incubation of HLM with chlorpyrifos. Chlorpyrifos inhibited the generation of carbaryl methylol, catalyzed predominately by CYP2B6, more than other pathways, correlating with an earlier observation that chlorpyrifos is metabolized to its oxon primarily by CYP2B6. Therefore, carbaryl metabolism in humans and its interaction with other chemicals is reflected by the concentration of CYP isoforms in HLM and their activities in the metabolic pathways for carbaryl. (Supported by NCDA Environmental Trust Fund)}, number={3}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Tang, J and Cao, Y and Rose, RL and Hodgson, E}, year={2002}, month={Oct}, pages={229–241} }
 @article{tang_cao_rose_brimfield_dai_goldstein_hodgson_2001, title={Metabolism of chlorpyrifos by human cytochrome P450 isoforms and human, mouse, and rat liver microsomes}, volume={29}, number={9}, journal={Drug Metabolism and Disposition}, author={Tang, J. and Cao, Y. and Rose, R. L. and Brimfield, A. A. and Dai, D. and Goldstein, J. A. and Hodgson, E.}, year={2001}, pages={1201–1204} }
 @article{dai_cao_falls_levi_hodgson_rose_2001, title={Modulation of mouse P450 isoforms CYP1A2, CYP2B10, CYP2E1, and CYP3A by the environmental chemicals mirex, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene, vinclozolin, and flutamide}, volume={70}, ISSN={["1095-9939"]}, DOI={10.1006/pest.2001.2551}, abstractNote={Abstract Several environmental chemicals are disruptive to the reproductive and endocrine systems of many species, including humans. Mechanisms for endocrine disruption are presently under scrutiny. Xenobiotic inducible mammalian cytochrome P450 (CYP) enzymes metabolize a variety of substrates including environmental chemicals, pesticides, and drugs. The metabolism, and thus the effect, of endogenous chemicals including steroid hormones, vitamins, etc. that are transformed by CYP enzymes can be influenced by environmental exposure to CYP-inducing chemicals. This study demonstrated that structurally diverse environmental chemicals including mirex, 2,2-Bis( p -chlorophenyl)-1,1-dichloroethylene (DDE), vinclozolin, and flutamide are capable of inducing several mouse liver CYP isozymes. As demonstrated by Western blotting, mirex induced CYP1A2, 2B10, 2E1, and 3A and vinclozolin induced 1A2 and 2B10. The only isoforms significantly induced by DDE and flutamide were 3A and 1A2, respectively. Since some of these isoforms are known to be involved in metabolism of endogenous hormones, we also studied the effects of these CYP inducers on testosterone metabolism and seminal vesicle weights. Mirex and DDE treatments had profound effects on the metabolism of testosterone, resulting in 2.5- to 3-fold more hydroxylated products than controls. Lesser, but significant, increases in specific metabolites of testosterone were also observed following treatment with vinclozolin and flutamide. Seminal vesicle weights were lower for all treatment groups except DDE. Results of this study demonstrate that, due to their CYP-inducing potential, these chemicals may significantly impact testosterone metabolism and this may be a contributing factor in their antiandrogenic effects.}, number={3}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={Dai, D and Cao, Y and Falls, G and Levi, PE and Hodgson, E and Rose, RL}, year={2001}, month={Jul}, pages={127–141} }
 @article{hodgson_rose_cao_dehal_kupfer_2000, title={Flavin-containing monooxygenase isoform specificity for the N-oxidation of tamoxifen determined by product measurement and NADPH oxidation}, volume={14}, ISSN={["1095-6670"]}, DOI={10.1002/(SICI)1099-0461(2000)14:2<118::AID-JBT8>3.0.CO;2-T}, abstractNote={The Km value for tamoxifen is 1.2 mM for mouse FMO1 (human FMO1 is not expressed in adults) and 1.4 mM for human FMO3, with no detectable activity being expressed toward tamoxifen by FMO5 from either mouse or human. These data are derived from experiments using 3H‐tamoxifen as substrate in which the product, tamoxifen N‐oxide, was measured directly. It was not possible to derive meaningful data from the measurement of NADPH consumption because Escherichia coli preparations, in the presence of tamoxifen, regardless of whether the E. coli was expressing an FMO isoform, consumed large amounts of NADPH without the appearance of tamoxifen N‐oxide or other discernable product. © 2000 John Wiley & Sons, Inc. J Biochem Toxicol 14: 118–120, 2000}, number={2}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Hodgson, E and Rose, RL and Cao, Y and Dehal, SS and Kupfer, D}, year={2000}, pages={118–120} }
 @article{hodgson_cherrington_coleman_liu_falls_cao_goldstein_rose_1998, title={Flavin-containing monooxygenase and cytochrome P450 mediated metabolism of pesticides: from mouse to human}, volume={2}, number={1998}, journal={Reviews in Toxicology}, author={Hodgson, E. and Cherrington, N. and Coleman, S. C. and Liu, S. and Falls, J. G. and Cao, Y. and Goldstein, J. E. and Rose, R. L.}, year={1998}, pages={231–243} }
 @article{cherrington_cao_cherrington_rose_hodgson_1998, title={Physiological factors affecting protein expression of flavin-containing monooxygenases 1, 3 and 5}, volume={28}, ISSN={["0049-8254"]}, DOI={10.1080/004982598239254}, abstractNote={1. The mouse and rat exhibit substantial differences in the gender expression of flavin-containing monooxygenase (FMO) forms. Hepatic FMO1 is gender-dependent in both species, selective to the male in rat, female in mouse. Human FMO1 is nearly undetectable. FMO3 in mouse is gender-specific to the female, but gender-independent in rat and man. FMO5 is gender-independent for mouse, rat and man. 2. Gender differences in substrate metabolism do not reflect overall FMO or isoform differences. Methimazole, imipramine and thiobenzamide are much better substrates for FMO1 than for FMO3 or FMO5. 3. Activities of microsomal samples toward these substrates reflect the relative abundance of FMO1. Hepatic samples show a 3-fold greater activity toward methimazole in the female mouse and male rat. Human microsomal samples show minimal activity. 4. Developmentally, FMO1 and FMO5 are expressed in foetuses as early as gestation days 15 and 17 and equally between genders until puberty. FMO3 is not found until 2 weeks post-partum and is found equally in the male and female until 6 weeks post-partum when it becomes undetectable in the male. 5. An event takes place after birth but before puberty that confers the ability to produce FMO3. The developmental pattern observed for mouse FMO3 is similar to human FMO3.}, number={7}, journal={XENOBIOTICA}, author={Cherrington, NJ and Cao, Y and Cherrington, JW and Rose, RL and Hodgson, E}, year={1998}, month={Jul}, pages={673–682} }
 @article{falls_ryu_cao_levi_hodgson_1997, title={Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex steroids}, volume={342}, ISSN={["0003-9861"]}, DOI={10.1006/abbi.1997.9965}, abstractNote={Based on enzyme activity, protein levels, and mRNA levels, we have previously demonstrated the female-predominant, female-specific, and gender-independent expression in mouse liver of FMO forms 1, 3, and 5, respectively. This study investigated the roles of testosterone, 17 beta-estradiol, and progesterone in the regulation of hepatic FMOs. FMO expression was examined in gonadectomized CD-1 mice, normal CD-1 mice receiving hormonal implants, and gonadectomized mice receiving various hormonal treatments. Following castration of males, hepatic FMO activity levels were significantly increased and serum testosterone levels significantly decreased; however, administration of physiological levels of testosterone to castrated animals returned FMO activity and testosterone concentrations to control levels. When sexually intact and ovariectomized female mice were treated with testosterone, their hepatic FMO activity levels were reduced to those of their male counterparts, concomitant with high serum testosterone levels. In males, castration dramatically increased FMO3 and FMO1 expression, and testosterone replacement to castrated males resulted in ablation of FMO3 expression. In addition, testosterone administration to females (sexually intact and gonadectomized animals) reduced FMO1 expression and obviated FMO3 expression. In females, ovariectomy alone slightly reduced FMO activity, indicative of a possible stimulatory role of female sex steroids; however, female FMO isozyme expression was relatively unchanged, and hormone replacement therapy to ovariectomized females had no discernible effect. In males and females, FMO5 levels were unaffected by gonadectomy or hormone administration, thus indicating a sex hormone-independent mechanism of regulation for this isoform. Interestingly, FMO1 protein levels were increased in sexually intact males following treatment with 17 beta-estradiol; however, only a slight increase in FMO3 protein level was observed. No positive hormone effectors of female FMO expression were identified.}, number={2}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Falls, JG and Ryu, DY and Cao, Y and Levi, PE and Hodgson, E}, year={1997}, month={Jun}, pages={212–223} }