Characterization of cytochrome P450-dependent dimethylhydrazine metabolism in human colon microsomes.
Polyclonal antibodies to components of the rat liver cytochrome P450 system were used to examine the composition and function of the microsomal cytochrome P450-dependent monooxygenase system of human colonic mucosal cells. Anticytochrome P450 reductase antibody gave a strong band of immunocross-reactivity in human colon microsomes at the same molecular weight level as purified cytochrome P450 reductase from rat liver, as well as hepatic microsomes isolated from untreated or phenobarbital-treated rats. These results demonstrate the presence of cytochrome P450 reductase in human colon cells. Similarly, cytochromes P450 IIB1 and IIA1 also appear to be present in Western blots of human colon microsomes. These antibodies, as well as antibodies to reductase and cytochrome b5, inhibit dimethylhydrazine metabolism in human colon microsomes to varying degrees. These data argue for a functional P450-dependent drug metabolism system in colon capable of activating/metabolizing the colon-specific model carcinogen, 1,2-dimethylhydrazine.
Stralka
D
D
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
Strobel
H W
HW
D019813:1,2-Dimethylhydrazine; D000818:Animals; D003106:Colon / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D004127:Dimethylhydrazines / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004127:Dimethylhydrazines; D007106:Immune Sera; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D019813:1,2-Dimethylhydrazine