Free radical generation from heterocyclic amines by cytochrome b5 reductase in the presence of NADH

We previously reported findings that NADPH/cytochrome P450 reductase can generate superoxide anion radical (O 2 − ) from heterocyclic amines (HCA) and from many anticancer agents in vitro. Here we present more evidence in which O 2 − is generated when recombinant human cytochrome b5 reductase (rh-Cy...

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Veröffentlicht in:	Cancer letters 1999-09, Vol.143 (2), p.117-121
Hauptverfasser:	Maeda, Hiroshi, Sawa, Tomohiro, Yubisui, Toshitugu, Akaike, Takaaki
Format:	Artikel
Sprache:	eng
Schlagworte:	Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Chemical agents Cytochrome b5 reductase Cytochrome Reductases - metabolism Cytochrome-B Reductase DNA Damage Electron spin resonance Free Radicals - metabolism Heterocyclic amines Humans Medical sciences NAD - metabolism NADH Quinolines - metabolism Quinoxalines - metabolism Recombinant Proteins - metabolism Superoxide generation Tumors
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Zusammenfassung:	We previously reported findings that NADPH/cytochrome P450 reductase can generate superoxide anion radical (O 2 − ) from heterocyclic amines (HCA) and from many anticancer agents in vitro. Here we present more evidence in which O 2 − is generated when recombinant human cytochrome b5 reductase (rh-Cytb5Rd) was incubated with HCAs such as IQ and MeIQ in the presence of NADH in vitro. This indicates that free radical generation by rh-Cytb5Rd in the presence of HCA may add new insight into the damage of DNA in addition to the previously known mechanism: interaction of activated HCA-intermediates to form DNA adduct.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/S0304-3835(99)00139-1