Hemin potentiates nitric oxide-mediated nitrosation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline

Heme has been reported to be an important contributor to endogenous N-nitrosation within the colon and to the enhanced incidence of colon cancer observed with increased intake of red meat. This study uses the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) as a target to evaluate hemin potentiation of nitric oxide (NO)-mediated nitrosation. Formation of 14C-2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N−NO−IQ) was monitored by HPLC following incubation of 10 μM IQ with the NO donor spermine NONOate (1.2 μM NO/min) at pH 7.4 in the presence or absence of hemin. N−NO−IQ formation due to autoxidation of NO was at the limit of detection (0.1 μM) and increased 22-fold in the presence of 10 μM hemin and an in situ system for generating H2O2 (glucose oxidase/glucose). A linear increase in N−NO−IQ formation was observed from 1 to 10 μM hemin. Significant nitrosamine formation occurred at fluxes of NO and H2O2 as low as 0.024 and 0.25 μM/min, respectively. Potentiation by hemin was not affected ...