Hormonal regulation of benzo[a]pyrene metabolism in human adrenocortical cell cultures.
In cultured fetal human adrenocortical cells, metabolism of the carcinogen benzo[a]pyrene was found to be unresponsive to the xenobiotic inducers 3-methylcholanthrene, benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, exposure of cultures to the hormone adrenocorticotropin (ACTH) for 48 hours stimulated benzo[a]pyrene metabolism 3-fold. The major metabolite was the 7,8-diol. Other compounds which stimulate the production of adrenocortical cell cyclic AMP (forskolin and cholera toxin) as well as monobutyryl cyclic AMP also increased benzo[a]pyrene metabolism. Human adrenocortical cells thus provide an unusual example of hormonal regulation of the metabolism of a carcinogen.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003994:Bucladesine / Q000031:analogs & derivatives / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin; D000242:Cyclic AMP / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology; D004622:Embryo, Mammalian; D006801:Humans; D007700:Kinetics
D002273:Carcinogens; D004224:Diterpenes; C002373:monobutyryl cyclic AMP; D005576:Colforsin; D001564:Benzo(a)pyrene; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP