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

Highly purified cytochrome P‐450 reductase (also called cytochrome c reductase; EC 1.6.2.4.) and NADPH were used to generate superoxide radical (O(2)) from 11 different heterocyclic amines (HCAs) as identified by electron spin resonance spectroscopy using the spin trapping method with 5,5‐dimethyl‐1...

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Detalles Bibliográficos
Autores principales: Sato, Keizo, Akaike, Takaaki, Kojima, Yuichiro, Ando, Masayuki, Nagao, Minako, Maeda, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1992
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918710/
https://www.ncbi.nlm.nih.gov/pubmed/1336493
http://dx.doi.org/10.1111/j.1349-7006.1992.tb02746.x
Descripción
Sumario:Highly purified cytochrome P‐450 reductase (also called cytochrome c reductase; EC 1.6.2.4.) and NADPH were used to generate superoxide radical (O(2)) 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(‐O(2)(−)) (i.e., the DMPO spin adduct of ‐O(2)(−)) was strongest for 2‐amino‐3,4‐dimethy]imidazo[4,5‐f]quinoline (MeIQ). The O(2)(−) 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; O(2)(−) generation was lowest with 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole CH(3)COOH (MeAαC). By using Lineweaver‐Burk plots, K(m) values of cytochrome P‐450 reductase for mitomycin C., IQ, and MeIQ were determined to be 1,60 × 10(−6) M, 1.97 × 10(−5)M, 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.