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
-
Send reprint requests to: Mitsukazu Kitada, Ph.D., Division of Pharmacy, Chiba University Hospital, 1–8-1 Inohana, Chuo-ku, Chiba 260, Japan.
-
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
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|