Multiple cytochrome P-450 subfamilies are co-induced with P-glycoprotein by both phenothiazine and 2-acetylaminofluorene in rats

Tomonori Tateishi, Hironori Nakura, Masako Asoh, Minoru Watanabe, Masami Tanaka, Toshio Kumai, Shinichi Kobayashi

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

We studied the effects of two P-glycoprotein (P-gp) inducers, 2-acetylaminofluorene (2-AAF) and phenothiazine (PTZ), administered intraperitoneally, on the activities and content of hepatic cytochrome P-450 (CYP) subfamilies in hepatic microsomes of Sprague-Dawley rats. After 4-day administration of 2-AAF or PTZ, the P-gp content was increased. The total CYP content after PTZ treatment was significantly increased compared with that of controls. The CYP1A, CYP2B and CYP3A2 contents were induced, while the CYP2C6, CYP2C11 and CYP2E1 contents remained unaffected. A marked increase in CYP1A1 was found after administration of each compound. Ethoxyresorufin O-deethylase, pentoxyresorufin O-deethylase, and testosterone 6β hydroxylation activities showed a significant increase after both 2-AAF and PTZ treatments. In particular, ethoxyresorufin O-deethylase exhibited more than ten times greater activity than that of the controls after the treatments. These results suggest that P-gp inducers affect several CYP subfamilies in addition to CYP3A, which is reported to be up-regulated coordinately with P-gp by a CYP3A inducer. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalCancer Letters
Volume138
Issue number1-2
DOIs
Publication statusPublished - Apr 26 1999
Externally publishedYes

Keywords

  • 2-Acetylaminofluorene
  • Cytochrome P-450 family
  • P-glycoprotein
  • Phenothiazine
  • Sprague-Dawley rat

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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