INFLUENCE OF ARYL GROUP ON REACTION OF GLUCURONIDES OF N-ARYLACETHYDROXAMIC ACIDS WITH POLYNUCLEOTIDES

Abstract

The reactions of the glucuronide conjugates of the carcinogens N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), N-hydroxy-4-acetylaminostilbene (N-hydroxy-AAS), N-hydroxy-4-acetylaminobiphenyl (N-hydroxy-AABP) and N-hydroxy-2-acetylaminophenanthrene (N-hydroxy-AAP) with [yeast] tRNA, rRNA, [rat liver] DNA, polyadenylate, polyguanylate, polyuridylate, polycytidylate, poly(adenylate, guanylate) and poly(guanylate, uridylate) were studied. The relative order of reactivity of these glucuronides with nucleic acids, measured by the covalent binding of the aryl group labeled with 3H or 14C, was glucuronide of N-hydroxy-AAF > glucuronide of N-hydroxy-AAS > glucuronide of N-hydroxy-AABP > glucuronide of N-hydroxy-AAP. The glucuronide of N-hydroxy-AAP showed only marginal or negligible reactivity. The glucuronide of N-hydroxy-AAF showed greater reactivity with polyguanylate than with polyadenylate, but the reverse was true for the glucuronide of N-hydroxy-AAS. Both of these glucuronides had lower extents of reaction with polyuridylate and polycytidylate. Except for the reaction of the glucuronide of N-hydroxy-AABP with polyadenylate, there was no detectable reaction of this glucuronide or the glucuronide of N-hydroxy-AAP with the homopolynucleotides. Under comparable conditions the glucuronide conjugates of N-hydroxy-AAF, N-hydroxy-AAS and N-hydroxy-AABP demonstrated greater reactivity with poly(adenylate, guanylate) and poly(guanylate, uridylate) than with the homopolynucleotides. Synthesis of 2 new glucuronide conjugates, those of N-hydroxy-AAS and N-hydroxy-AAP, is described.