Evidence of Direct Generation of Oxygen Free Radicals from Heterocyclic Amines by NADPH/Cytochrome P‐450 Reductase in vitro

Keizo Sato, Takaaki Akaike, Yuichiro Kojima, Masayuki Ando, Minako Nagao, Hiroshi Maeda

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41 Citations (Scopus)

Abstract

Highly purified cytochrome P‐450 reductase (also called cytochrome c reductase; EC 1.6.2.4.) and NADPH were used to generate superoxide radical (O2) from 11 different heterocyclic amines (HCAs) as identified by electron spin resonance spectroscopy using the spin trapping method with 5,5‐dimethyl‐1‐pyrroline JV‐oxide (DMPO). The signal intensity of DMP0‐OOH(‐O2) (i.e., the DMPO spin adduct of ‐O2) was strongest for 2‐amino‐3,4‐dimethy]imidazo[4,5‐f]quinoline (MeIQ). The O2 generation with HCAs decreased in the following order: 2‐amino‐3,8‐dimethyI‐imidazo[4,5‐f] quinoxaline (MeIQx) = 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) > 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline (diMeIQx) ≥ other HCAs; O2 generation was lowest with 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole CH3COOH (MeAαC). By using Lineweaver‐Burk plots, Km values of cytochrome P‐450 reductase for mitomycin C., IQ, and MeIQ were determined to be 1,60 × 10−6 M, 1.97 × 10−5M, and 2.83 × 10−6 M, respectively. The present findings have important implications for carcinogenesis because of the known effect of oxygen radicals on cell proliferation.

Original languageEnglish
Pages (from-to)1204-1209
Number of pages6
JournalJapanese Journal of Cancer Research
Volume83
Issue number11
DOIs
Publication statusPublished - 1992 Nov

Keywords

  • ESR spin trapping
  • Heterocyclic amine
  • NADPH/cytochrome P‐450 reductase Carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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