DNA adduct formation of hepatocarcinogenic aromatic amines in rat liver: effect of cytochrome P450 inducers

Masakuni Degawa, Misaki Kojima, Kouichi Yoshinari, Mariko Tada, Yoshiyuki Hashimoto

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

F344 rats were treated with an i.p. injection of 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole (Glu P-1) or 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and examined for the formation of the DNA adduct in the liver. To examine the effect of pretreatment with a cytochrome P450 (CYP) inducer on the formation of DNA adduct, these rats were pretreated with 3-methylcholanthrene (MC; CYP1A1/1A2 inducer) or phenobarbital (PB; CYP2B inducer). Administration of Glu P-1 and 3-MeO-AAB gave 2 and 5 adducts, respectively, as determined by 32P-postlabeling assay. By Glu P-1 administration, pretreatment of rats with MC, but not with PB, increased the total amount of DNA adducts including 3 new adducts as minor products. In contrast, pretreatment of rats with PB increased the total amount of DNA adducts derived by 3-MeO-AAB. The increase of aromatic amine DNA adducts by pretreatment with a CYP inducer was proportional to the activity of induced CYP isosyme(s) responsible for the mutagenic activation of each aromatic amine.

Original languageEnglish
Pages (from-to)77-81
Number of pages5
JournalCancer Letters
Volume79
Issue number1
DOIs
Publication statusPublished - 1994 Apr 29

Keywords

  • 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole
  • 3-methoxy-4-amino-azobenzene
  • Cytochrome P450
  • DNA adduct
  • P-Postlabeling
  • Rat liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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