title: Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine N-demethylation.
abstract: The N-demethylation of dacarbazine in liver microsomes was significantly increased by treatment of rats with beta-naphthoflavone, dexamethasone, or phenobarbital. However, the extent of increase in the N-demethylation observed in beta-naphthoflavone-treated rats was much greater than that observed in dexamethasone-treated rats. A good correlation between N-demethylation of dacarbazine and O-deethylation of phenacetin was observed when a low concentration of phenacetin was used. Furthermore, the activity of dacarbazine N-demethylase in rat liver microsomes was highly correlated with the amounts of CYP protein immunochemically determined with anti-rat CYP1A2 antibodies. In addition, antibodies to rat CYP1A2, and furafylline and alpha-naphthoflavone, which are known inhibitors of CYP1A enzymes, exhibited inhibitory effects on dacarbazine N-demethylation. These results indicated that CYP1A enzymes may be responsible for N-demethylation of dacarbazine in rat liver microsomes.
authors.forename: S
authors.initials: S
authors.lastname: Yamagata
authors.forename: S
authors.initials: S
authors.lastname: Ohmori
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Yoshino
authors.forename: M
authors.initials: M
authors.lastname: Hino
authors.forename: I
authors.initials: I
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Kitada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003606:Dacarbazine / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D003577:Cytochrome P-450 Enzyme System; D019388:Cytochrome P-450 CYP1A2