Induction of Repair Synthesis of DNA in Mammary and Urinary Bladder Epithelial Cells by W-Hydroxy Derivatives of Carcinogenic Arylamines1

Unscheduled DNA synthesis (UDS)-inducing activity was used as a parameter to estimate the abilities of rat mammary epithelial cells and urothelial cells from various species to activate carcinogenic aromatic amine derivatives. The A'-hydroxy, A'-hydroxy-A'-acetyl, A'-hydroxy-A'glucuronosyl derivatives of 2-aminofluorene (2-AF) and 4-aminobiphenyl (4-ABP) induced UDS in primary cultures of rat mammary epithelial cells, but 2-AF, the 0-glucuronide of /V-hydroxyWV-acetyl-2-AF(N-OHAAF) and 4-ABP did not. Neither the activity of N-OH-AAF, Nhydroxy-yV-formyl-2-AF, nor Ar-acetoxy-A'-acetyl-2-AF was significantly altered by paraoxon, an inhibitor of microsomal /V-deacetylase. Although A'-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMABP) also in duced UDS, its .V-acctyl derivative, which can not be activated by intramolecular Af.O-acetyltransfer, did not. Similarly, rat urothelial cells were responsive to the UDS-inducing activity of this hydroxylamine, but not the hydroxamic acid. In contrast, dog urothelial cells were responsive to both compounds. The UDS-inducing activity of N-OH-AAF was inhibited by paraoxon in the dog, but not in rat urothelial cells. ,VHydroxy-A',A"-diacetyIbenzidine induced UDS in the urothelial cells of dog, rat, and rabbit, and a human urothelial cell line, HCV-29, whereas benzidine, A'-acetylbenzidine, and A^'-diacetylbenzidine did not. Cotreatment with 12-0-tetradecanoylphorbol-13-acetate did not enable ben zidine to induce UDS in dog urothelial cells. Rat mammary epithelial cells activated N-OH-DMABP by acetyl coenzyme A-dependent (>acetylation and N-OH-AAF by JV,O-acetyltransfer. They could not Ndeacetylate N-OH-AAF. These results suggest that rat mammary and bladder epithelial cells are capable of activating A'-arylhydro\) lamine metabolites of these carcinogens, probably by A'.O-acetyltransfer and Oacetylation, whereas dog urothelial cells are more likely to activate these metabolites by jV-deacetylation and a reaction that has yet to be identified.