the effects of putative dna repair inhibitors on dna adduct levels and unscheduled dna synthesis in rat hepatocytes exposed to 2acetylaminofluorene the enzymology of dna repair is currently under active investigation the purpose of the present study was to examine the involvement of a number of enzymes dna polymerase alpha and beta dna topoisomerase ii and ribonucleotide reductase in the repair of chemically induced dna damage in a mammalian cell system this was done by studying the effects of inhibitors of these enzymes on the levels of 2acetylaminofluorene 2aafdna adducts and on the induction of uds in primary cultures of rat hepatocytes exposed to the carcinogen in vitro the results obtained with aphidicolin an inhibitor of dna polymerase alpha show that the binding of 2aaf to cellular dna was significantly higher in samples exposed to this compound moreover induction of uds by 2aaf was completely blocked in the presence of this compound dideoxythymidine a dna polymerase beta inhibitor led to complex results it produced a reduced dnaspecific activity due to 3h2aaf adduct formation as well as a diminished but still detectable uds response in the presence of 2aaf inhibitors of dna topoisomerase ii nalidixic acid and ribonucleotide reductase hydroxyurea did not cause any statistically significant change in the accumulation of 2aaf adducts nor did they affect the induction of uds the data clearly suggest that dna polymerase alpha participates in the repair of 2aaf adducts in hepatocytes in addition neither dna topoisomerase ii activity nor limitations in the precursor nucleotide pools appear to be critical factors in this process