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.
D000478:Alkylation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D016685:Mitomycin; D008937:Mitomycins / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D008937:Mitomycins; D009153:Mutagens; D016685:Mitomycin; D004247:DNA