Adducts from the reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene with deoxyguanosine or DNA in vitro and from hepatic DNA of mice treated with N-methyl- or N,N-dimethyl-4-aminoazobenzene.
N-Benzoyloxy-N-methyl-4-aminoazobenzene, a synthetic model ultimate carcinogenic derivative of N-methyl- and N,N-dimethyl-4-aminoazobenzene, reacted with [8-14C]deoxyguanosine in vitro to yield ten 14C-containing products separable by high-performance liquid chromatography. N-(Deoxyguanosin-8-yl)-N-methyl-4-aminoazobenzene, previously characterized as the major adduct formed in this reaction, occurred as cis and trans isomers which were interconvertible and together accounted for 75% of the reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene with [8-14C]deoxyadenosine. The products obtained by reaction of DNA with N-benzoyloxy-N-methyl-4-aminoazobenzene and subsequent digestion to deoxynucleosides had a profile similar to that of the products obtained from deoxyguanosine except that the DNA digest contained a second major product that was formed in only small amounts on reaction with deoxyguanosine. The latter product has been identified as 3-(deoxy-guanosin-N2-yl)-N-methyl-4--aminoazobenzene by Beland et. al. (Chem.-Biol. Interactions, in press). Reaction with [purine-14C]DNA showed that most, if not all, of the products were derived from purine nucleosides. Digests of the DNA from the livers of C57BL/6 X C3H/He F1 mice, given injections at 12 days of age with [prime ring-3H]N-methyl- or N,N-dimethyl-4-aminoazobenzene, contained the same major adducts as did those obtained from DNA reacted with N-benzoyloxy-N-methyl-4-aminoazobenzene. The hepatic DNA  also yielded a series of minor products that comigrated on high-performance liquid chromatography with adducts obtained in the reactions with N-benzoyloxy-N-methyl-4-aminoazobenzene. Approximately 70 and 30%, respectively, of the N-(deoxyguanosin-8-yl)-N-methyl-4-aminoazobenzene and of the second major product were removed from the mouse liver DNA within 10 days after administration of [prime ring-3H]N,N-dimethyl-4-aminoazobenzene. These data are of interest in view of the development of multiple hepatic tumors in mice of this hybrid treated prior to weaning with N-methyl- or N,N-dimethyl-4-aminoazobenzene.
D000818:Animals; D001391:Azo Compounds / Q000008:administration & dosage*; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine; D005260:Female; D007267:Injections; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010128:p-Aminoazobenzene / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000032:analysis
D001391:Azo Compounds; D002273:Carcinogens; D010128:p-Aminoazobenzene; C009728:N-benzoyloxy-N-methyl-4-aminoazobenzene; D004247:DNA; D003849:Deoxyguanosine