ADDUCTS FROM THE REACTION OF N-BENZOYLOXY-N-METHYL-4-AMINOAZOBENZENE WITH DEOXYGUANOSINE OR DNA INVITRO AND FROM HEPATIC DNA OF MICE TREATED WITH N-METHYL- OR N,N-DIMETHYL-4-AMINOAZOBENZENE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2493-2499
Abstract
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 10 14C-containing products separable by high-performance liquid chromatography. N-(Deoxyguanosine-8-yl)-N-methyl-4-aminoazobenzene, the major adduct in this reaction, occurred as interconvertible cis and trans isomers which together accounted for 75% of the reaction products. Only 1 minor product was obtained on 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 2nd major product formed in only small amounts on reaction with deoxyguanosine. The latter product was 3-(deoxy-guanosin-N2-yl)-N-methyl-4-aminoazobenzene. 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 2nd 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.

This publication has 11 references indexed in Scilit: