PT  - JOURNAL ARTICLE
AU  - Shin-ichi Yamagata
AU  - Shigeru Ohmori
AU  - Naoko Suzuki
AU  - Masaki Yoshino
AU  - Mayuko Hino
AU  - Itsuko Ishii
AU  - Mitsukazu Kitada
TI  - Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine <em>N</em>-demethylation
DP  - 1998 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 379--382
VI  - 26
IP  - 4
4099  - http://dmd.aspetjournals.org/content/26/4/379.short
4100  - http://dmd.aspetjournals.org/content/26/4/379.full
SO  - Drug Metab Dispos1998 Apr 01; 26
AB  - 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