Altered Expression of Hepatic CYP1A Enzymes in Rat Hepatocarcinogenesis

Masakuni Degawa, Shin‐ichi ‐i Miura, Kouichi Yoshinari, Yoshiyuki Hashimoto

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13 Citations (Scopus)

Abstract

Hyperplastic nodules of the liver were induced by treating male F344 rats with a combination of diethylnitrosamine and partial hepatectomy. The livers were examined for the expression of cytochrome P450 (CYP) enzymes, mainly CYP1A1 and CYP1A2; the amount and activity of the enzymes in the nricrosomes were assessed by enzymatic and immunological methods. Levels of CYP1A mRNAs were assayed by Northern blotting. In the liver bearing hyperplastic nodules, the total amount of microsomal CYP enzymes decreased to about 50% of the control. The microsomal activities for the CYP1A2‐mediated activation of carcinogenic heterocyclic amines decreased to about 20% of the corresponding controls, in association with decreases in the levels of mRNA and protein of CYP1A2. Furthermore, the inducibility of CYP1A2 by CYP1A inducers such as 3‐methoxy‐4‐aminoazobenzene and 3‐methylcholanthrene was also decreased at the mRNA, protein and activity levels. On the other hand, CYP1A1 enzyme, which was undetectable in control rat liver, appeared in the liver bearing hyperplastic nodules, but its inducibility by a CYP1A inducer decreased slightly. The present findings indicated that individual CYP1A enzymes are differently regulated, and the expression of CYP1A2 is reduced preferentially in the liver bearing hyperplastic nodules.

Original languageEnglish
Pages (from-to)535-539
Number of pages5
JournalJapanese Journal of Cancer Research
Volume86
Issue number6
DOIs
Publication statusPublished - 1995 Jun

Keywords

  • Altered expression
  • CYP1A
  • Cytochrome P450
  • Hepatocarcinogenic process
  • Rat liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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