Fig. 1
Generation of free radicals by infection and by heterocyclic amine (HCA), and generation of nitrated bases and mutation in Sendai virus via NO. Pathways a, c and d are involved in infection-induced inflamed tissue involving induction of inducible form of nitric oxide synthase (iNOS), and subsequently generation of nitric oxide (NO) and superoxide (O ·−2 ) and then peroxynitrite (ONOO−), which nitrated guanine (→ 8-nitroguanine), and 8-nitroguanosine (NitroGuo), as substrates of NOS or cytochrome c reductase, thereby generation of O ·−2 . The total system progressively produces O ·−2 , with stoichiometry of greater than 1:1 [51, 100, 108]. b Generation of O ·−2 from heterocyclic amine (HCA) in the presence of cytochrome (Cyt) P450 reductase and NADPH, resulting in DNA damage, cleavage and mutation. c NADPH cytochrome P450 reductase would generates O ·−2 most effectively from nitroguanosine among other base-modified derivatives [57,58,59,60,61]. d Shows the NO dependence of viral mutation. *, **, significant changes in % viral mutations in B6 mice, in comparison with iNOS knockout mice by time. ** statistical significance (< 0.01). See text