Characterization of DNA adducts of the carcinogen N-methyl-4-aminoazobenzene in vitro and in vivo.
Since the susceptibility of specific tissues to tumor formation has been correlated with the persistence of DNA-carcinogen adducts, the identity and persistence of DNA adducts formed from the hepatocarcinogen N-methyl-4-aminoazobenzene (MAB) has been determined. The synthetic ultimate carcinogen N-benzoyloxy-N-methyl-4-aminoazobenzene (N-BxO-MAB) was reacted in vitro with either calf thymus or rat liver DNA to yield approx. 1 bound residue per 1000 nucleotides. After enzymatic hydrolysis of the DNA and high pressure liquid chromatographic analysis, at least six MAB adducts were detected. Two of the products cochromatographed with MAB-DNA adducts formed in rat liver in vivo following oral administration of the precarcinogen MAB. These two adducts were identified by mass, UV and nuclear magnetic resonance (NMR) spectroscopy as N-(deoxyguanosin-8-yl)- and 3-(deoxyguanosin-N2-yl)-MAB. The former adduct was initially the predominant product in vivo, but it could not be detected 7 days following treatment. The latter adduct remained at a constant level for 14 days and therefore appears to be a persistent lesion.
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D008099:Liver; D008297:Male; D051381:Rats; D013950:Thymus Gland; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism*
D001391:Azo Compounds; D010128:p-Aminoazobenzene; C009728:N-benzoyloxy-N-methyl-4-aminoazobenzene; C005202:N-methyl-4-aminoazobenzene; D004247:DNA