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Metabolic nitrite formation from N-nitrosamines: evidence for a cytochrome P-450 dependent reaction
1Section of Toxicology, Institute of Pharmacology Obere Zahlbacher Str. 67, D-6500 Mainz
2Institute of Physiological Chemistry, University of the Saarland D-6650 Homburg, FRG
Nitrite was formed on incubation of N-nitrosamines with a reconstituted monooxygenase system, consisting of cytochrome P-450 (P-450) and NADPH P-450 reductase from pig liver. Nitrite was not obtained when the nitrosamines were incubated with NADPH P-450 reductase alone or when molecular oxygen or NADPH were omitted. Interaction of nitrosamines with the reconstituted P-450 system or with hemoglobin under reducing conditions resulted in optical spectra identical with those obtained with nitrite. It is proposed that N-nitrosamines are denitrosated by electron transfer from the hemoprotein iron to the nitrosamine molecule.
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