Regulation of cytochrome P450 in cultured human colonic cells.
The consequences of altered cytochrome P450-dependent monooxygenase activities in colonic tissue are unknown. As an initial step toward elucidating underlying mechanisms that regulate cytochrome P450 levels in colonic epithelium, we have characterized CYP1A1(3) induction in cultured human colonic cells (Caco-2). The induction of CYP1A1 by several inducers was measured by enzymatic activity and immunoreactivity. 3-Methylcholanthrene, beta-naphthoflavone, and benz[alpha]anthracene were strong inducers of CYP1A1, benzo[alpha]pyrene induced CYP1A1 activity only weakly, while benzo[e]pyrene and phenobarbital were essentially inactive as inducers. The response of Caco-2 cells to beta-naphthoflavone is similar to that previously observed in vivo in the rat colonic epithelium. In addition, we have demonstrated that this induction results from an increase in CYP1A1 transcriptional activity. These results suggest that the Caco-2 cell line exhibits certain characteristics of cytochrome P450 activity observed in colonic epithelium and may serve as a model for studying cytochrome P450-dependent activity in this tissue. The identification of a colonic cell line that responds to xenobiotic inducers will be useful for examining mechanisms of cytochrome P450 induction in the colon and elucidating the potential role of this system in colonic carcinogenesis.
Rockefeller University, New York, New York.
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D000230:Adenocarcinoma / Q000201:enzymology*; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D003110:Colonic Neoplasms / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; C026487:benzo(e)pyrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D010634:Phenobarbital