Identification of the DNA adducts formed in vitro from N-benzoyloxy-N-methyl-4-aminoazobenzene and in rat liver in vivo after administration of N-methyl-4-aminoazobenzene.
The synthetic model ultimate carcinogen N-benzoyloxy-N-methyl-4-aminoazobenzene reacted in vitro with either calf thymus or rat liver DNA to yield approximately 1 bound residue per 1,000 nucleotides. The DNA was enzymatically hydrolyzed and subjected to high-pressure liquid chromatographic analysis which indicated the presence of at least 6 N-methyl-4-aminoazobenzene (MAB) adducts. 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 UV, mass, and nuclear magnetic resonance spectroscopy as N-(deoxyguanosin-8-yl)- and 3-(deoxyguanosin-N(2)-yl)-MAB: the first adduct was initially the predominant product in vivo, ut it could not be detected 7 days after treatment, and the second remained at a constant level for 14 days and therefore appeared to be a persistent lesion.
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D001711:Biotransformation; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D051381:Rats; D013053:Spectrophotometry; 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