Chemical modification of DNA with muta-carcinogens. III. Reductive alkylation of DNA with mitomycin C.

Mitomycin C (MMC) binds to DNA after its reductive activation by catalytic hydrogenation with Pd on charcoal. Three modified nucleotides, named MG-1, MG-2, and MA, were isolated from the modified DNA after enzymatic hydrolysis to 5'-nucleotides. The structures of these modified nucleotides were deduced from their 1H-NMR and UV spectra, and from studies of the chemically transformed derivatives (hydrolysis, methylation, diazotization, and thioketonization). These three modified nucleotides were concluded to be 1,2-trans-2,7-diamino-1-(N2-deoxyguanylyl)mitosene (MG-1), 2,7-diamino-1-(O6-deoxyguanylyl)mitosene (MG-2) and 2,7-diamino-1-(N6-deoxyadenylyl)mitosene (MA). The same modified nucleotides were identified in DNA extracted from the livers of rats treated with MMC.