Abstract
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.
Footnotes
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Send reprint requests to: Mitsukazu Kitada, Ph.D., Division of Pharmacy, Chiba University Hospital, 1–8-1 Inohana, Chuo-ku, Chiba 260, Japan.
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This work was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
- Received July 22, 1997.
- Accepted December 3, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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