@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_usmani_hodgson_rose_2004, title={In vitro metabolism of fipronil by human and rat cytochrome P450 and its interactions with testosterone and diazepam}, volume={147}, ISSN={["1872-7786"]}, DOI={10.1016/j.cbi.2004.03.002}, abstractNote={Fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) is a highly active, broad spectrum insecticide from the phenyl pyrazole family, which targets the γ-amino butyric acid (GABA) receptor. Although fipronil is presently widely used as an insecticide and acaricide, little information is available with respect to its metabolic fate and disposition in mammals. This study was designed to investigate the in vitro human metabolism of fipronil and to examine possible metabolic interactions that fipronil may have with other substrates. Fipronil was incubated with human liver microsomes (HLM) and several recombinant cytochrome P450 (CYP) isoforms obtained from BD Biosciences. HPLC was used for metabolite identification and quantification. Fipronil sulfone was the predominant metabolite via CYP oxidation. The Km and Vmax values for human liver microsomes are 27.2 μM and 0.11 nmol/mg protein min, respectively; for rat liver microsomes (RLM) the Km and Vmax are 19.9 μM and 0.39 nmol/mg protein min, respectively. CYP3A4 is the major isoform responsible for fipronil oxidation in humans while CYP2C19 is considerably less active. Other human CYP isoforms have minimal or no activity toward fipronil. Co-expression of cytochrome b5 (b5) is essential for CYP3A4 to manifest high activity toward fipronil. Ketoconazole, a specific inhibitor of CYP3A4, inhibits 78% of the HLM activity toward fipronil at a concentration of 2 μM. Oxidative activity toward fipronil in 19 single-donor HLMs correlated well with their ability to oxidize testosterone. The interactions of fipronil and other CYP3A4 substrates, such as testosterone and diazepam, were also investigated. Fipronil metabolism was activated by testosterone in HLM but not in CYP3A4 Supersomes®. Testosterone 6β-hydroxylation in HLM was inhibited by fipronil. Fipronil inhibited diazepam demethylation but had little effect on diazepam hydroxylation. The results suggest that fipronil has the potential to interact with a wide range of xenobiotics or endogenous chemicals that are CYP3A4 substrates and that fipronil may be a useful substrate for the characterization of CYP3A4 in HLM.}, number={3}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Tang, J and Usmani, KA and Hodgson, E and Rose, RL}, year={2004}, month={Apr}, pages={319–329} }
 @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{dai_tang_rose_hodgson_bienstock_mohrenweiser_goldstein_2001, title={Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos}, volume={299}, number={3}, journal={Journal of Pharmacology and Experimental Therapeutics}, author={Dai, D. and Tang, J. and Rose, R. and Hodgson, E. and Bienstock, R. J. and Mohrenweiser, H. W. and Goldstein, J. A.}, year={2001}, pages={825–831} }
 @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} }