Effect of dexamethasone on cytochrome P-450 mediated metabolism of 2-acetylaminofluorene in cultured rat hepatocytes.

摘要: The metabolism of 2-acetylaminofluorene (AAF) to its six oxidative metabolites has been used investigate the effect dexamethasone on cytochrome P-450 activity in cultured rat hepatocytes. In control hepatocytes AAF 1-, 5-, 7-, 9- and N-hydroxylated rapidly declined culture over first 24 hr while 3-hydroxylation remained relatively constant. These activities either unchanged or increased slightly during next 48 culture. addition (100 nM) medium had little arresting initial decline but by 72 5- 3-hydroxylations values 2.5, 16 21 times respective 24-hr values. inductive 3- 5-hydroxylations was maximal at 100 nM whereas 7-hydroxylation linearly as a function concentration up 1 microM. Cortisol corticosterone non-glucocorticoids fluoxymesterone methyltestosterone induced pattern resembling that dexamethasone-treated cultures, suggesting range steroids not restricted glucocorticoids may induce multiple isozymes via related mechanisms. Pregnenolone alpha-carbonitrile only probably reflecting induction P-450p. While strong inducer hepatocyte culture, assay these freshly isolated cells after vivo treatment with showed small effects 5-hydroxylations. Indeed profile resembles more closely 3-methylcholanthrene vivo. data suggest factors yet be identified strongly influence steroid-induced gene expression.