Decreased pulmonary drug metabolism in mice treated with the PCB metabolite 4-methylsulphonyl-2,2',5,5'-tetrachlorobiphenyl.
4-Methylsulphonyl-2,2',5,5'-tetrachlorobiphenyl (4-MeSO2-TCB) is a major polychlorinated biphenyl (PCB) metabolite present in lung tissue of PCB-exposed human subjects. After treatment of mice with 4-MeSO2-TCB (100 mg/kg), the pulmonary N-demethylation of aminopyrine in vitro was significantly decreased, while hepatic N-demethylation was concomitantly increased, as compared to tissue from control mice. Treatment of mice with 4-MeSO2-TCB also decreased the in vivo pulmonary covalent binding of o,p'-DDD, while the in vivo hepatic covalent binding was increased. The results indicate that 4-MeSO2-TCB inhibits or represses a cytochrome P-450-dependent enzyme activity in the mouse lung, while in contrast this activity is induced in the mouse liver.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008939:Mitotane / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*
D065607:Cytochrome P-450 Enzyme Inhibitors; D000632:Aminopyrine; C050541:4-methylsulfonyl-2,2',5,5'-tetrachlorobiphenyl; D008939:Mitotane; D011078:Polychlorinated Biphenyls