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Rapid CommunicationShort 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
Drug Metabolism and Disposition April 1998, 26 (4) 379-382;
Shin-ichi Yamagata
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Shigeru Ohmori
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Naoko Suzuki
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Masaki Yoshino
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Mayuko Hino
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Itsuko Ishii
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Mitsukazu Kitada
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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
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Drug Metabolism and Disposition
Vol. 26, Issue 4
1 Apr 1998
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Rapid CommunicationShort 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
Drug Metabolism and Disposition April 1, 1998, 26 (4) 379-382;

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Rapid CommunicationShort 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
Drug Metabolism and Disposition April 1, 1998, 26 (4) 379-382;
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