Expression of two cytochromes P450 involved in carcinogen activation in a human colon cell line.
Cytochrome P450 is known to cause carcinogen activation and correspondingly increased cancer risk in animal models. In order to determine whether P450 in the colon may be involved in cancer development in the human, the human colon cell line LS174T was examined for the presence of various cytochromes P450. Two isozymes of P450 were identified in the human cell line. Expression of P450IA1 or IA2 was increased by treatment of the cell line with benzanthracene; the induction was demonstrated by an increase in RNA hybridizing to a probe for P450IA1 and by ethoxyresorufin deethylation activity. Western analysis of microsomes isolated from human colon tissue also demonstrated the presence of P450IA1, as well as a form which cross-reacted to an antibody to human P450IIC9. Another isozyme, P450IIE1, was identified by polymerase chain reaction amplification of RNA from LS174T cells. These results underscore the presence of cytochromes P450 in colonic tissue and provide a basis for the involvement of isozyme-specific P450 mediated reactions in carcinogenesis of the colon.
White
T B
TB
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
Hammond
D K
DK
Vásquez
H
H
Strobel
H W
HW
D000818:Animals; D001483:Base Sequence; D001551:Benz(a)Anthracenes / Q000494:pharmacology / Q000633:toxicity; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects / Q000201:enzymology; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004127:Dimethylhydrazines / Q000494:pharmacology / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D019324:beta-Naphthoflavone
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D002273:Carcinogens; D004127:Dimethylhydrazines; D007527:Isoenzymes; D012333:RNA, Messenger; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating