N-substitution of carbon 8 in guanosine and deoxyguanosine by the carcinogen N-benzoyloxy-N-methyl-4-aminoazobenzene in vitro.
The major reaction products of the carcinogenic electrophile N-benzoyloxy-N-methyl-4-aminoazobenzene with guanosine or deoxyguanosine were characterized as N-(guanosin-8-yl)- and N-(DEOXYGUANOSIN-8-YL)-N-methyl-4-aminoazobenzene from the following chemical, radiochemical, and spectroscopic studies: (a) the presence of equimolar amounts of both N-methyl-4-aminoazobenzene (MAB) and guanosine or deoxyguanosine residues was shown by the 3H:14C ratios of the products from the reaction of (prime ring-3H)-N-benzoyloxy-N-methyl-4-aminoazobenzene with (8-14C)guanosine or (8-14C)deoxyguanosine and by the molecular weights of the trimethylsilyl derivatives of both products: (b) substitution of the dye residue on its amino nitrogen was indicated by the retention in the products of the 3H:14C ration of (CH2-3H + 14CH3)-N-BENZOYLOXY-N-methyl-4-aminoazobenzene and by the release of MAB on treatment of the nucleoside-dye derivatives with strong alkali in air; (c) substitution of the guanine residues in positon 7 or 8 was demonstrated by loss of 3H from (8-3H)guanosine or (8-3H)deoxyguanosine in the formation of the nucleoside-dye derivatives; (d) the stability of the products to mild alkali (as contrasted to the lability of 7-alkylguanosines) provided strong evidence that the substitution was in position 8 of the guanine residue; (e) direct evidence of 8-substitution came from the acid hydrolysis of guanosinyl- and deoxyguanosinyl-N-methyl-4-aminoazo benzene to N-(guan-8-yl)-N-methyl-4-aminoazobenze in up to 50% yield; (f) comparisons of the proton or 13C nuclear magnetic resonance spectra or both of N-(guan-8-yl)- N-methyl-4-aminoazobenzene, MAB, N-(guanosin-8-yl)-2-acetylaminofluorene, 2-acetylaminofluorene, guanosine, and 7 -methylguanosine with the spectra of the guanosine-MAB product further confirmed that substitution had occurred at position 8 of the guanosine residue. The new compound N-(guan-8-yl)-N-methyl-4-aminoazobenzene was synthesized. Attempts to devise an unambiguous synthesis of N-(GUANOSIN-8-YL)-N-methyl-4-aminoazobenzene were not successful.
D000588:Amines; D001391:Azo Compounds; D001565:Benzoates; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D003853:Deoxyribonucleosides; D006151:Guanosine / Q000031:analogs & derivatives; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008970:Molecular Weight; D013055:Spectrophotometry, Infrared; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives
D000588:Amines; D001391:Azo Compounds; D001565:Benzoates; D002273:Carcinogens; D003853:Deoxyribonucleosides; D006151:Guanosine; D010128:p-Aminoazobenzene; C009728:N-benzoyloxy-N-methyl-4-aminoazobenzene