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Vol. 26, Issue 4, 379-382, April 1998

SHORT COMMUNICATION
Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine N-demethylation

Shin-ichi Yamagata, Shigeru Ohmori, Naoko Suzuki, Masaki Yoshino, Mayuko Hino, Itsuko Ishii, and Mitsukazu Kitada

Division of Pharmacy, Chiba University
Hospital (S.Y., S.O., N.S., M.K.) and
Laboratory of Clinical Pharmacology,
Faculty of Pharmaceutical Sciences,
Chiba University (M.Y., M.H., I.I.)

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.

Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.