V79 Chinese hamster cells express cytochrome P-450 activity after simultaneous exposure to polycyclic aromatic hydrocarbons and aminophylline.
V79 Chinese hamster lung cells expressed low but significant aryl hydrocarbon hydroxylase activities when treated with an inducer of cytochrome P-450I, such as benz[alpha]anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), together with aminophylline. Inducibility by polycyclic aromatic hydrocarbons and inhibition by a specific monoclonal antibody indicated that the observed enzyme activity was mediated by cytochrome P-450I. Intact V79 cells pretreated with TCDD and aminophylline for 24 h metabolized benzo[alpha]pyrene to phenolic products which accumulated linearly in the growth medium for at least the same time period. Exposure of V79 cells to 10 microM benzo[alpha]pyrene and aminophylline for 72 h reduced subsequent cell growth by about 40%. The results demonstrate that V79 cells, under specific conditions, express PAH-inducible cytochrome P-450I and are capable of activating benzo[alpha]pyrene to cytotoxic products.
GSF-Institut für Toxikologie, Neuherberg, F.R.G.
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F
Kiefer
F J
FJ
Wiebel
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*
D001551:Benz(a)Anthracenes; D000072317:Polychlorinated Dibenzodioxins; D011083:Polycyclic Compounds; D000628:Aminophylline; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D001189:Aryl Hydrocarbon Hydroxylases