TY - JOUR T1 - Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine <em>N</em>-demethylation JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 379 LP - 382 VL - 26 IS - 4 AU - Shin-ichi Yamagata AU - Shigeru Ohmori AU - Naoko Suzuki AU - Masaki Yoshino AU - Mayuko Hino AU - Itsuko Ishii AU - Mitsukazu Kitada Y1 - 1998/04/01 UR - http://dmd.aspetjournals.org/content/26/4/379.abstract N2 - The N-demethylation of dacarbazine in liver microsomes was significantly increased by treatment of rats with β-naphthoflavone, dexamethasone, or phenobarbital. However, the extent of increase in the N-demethylation observed in β-naphthoflavone-treated rats was much greater than that observed in dexamethasone-treated rats. A good correlation betweenN-demethylation of dacarbazine andO-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 α-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. The American Society for Pharmacology and Experimental Therapeutics ER -