2-acetylaminofluorene-induced unscheduled DNA synthesis in hepatocytes isolated from 3-methylcholanthrene treated...

The dose-dependent induction of unscheduled DNA synthesis (UDS) by 2-acetylaminofluorene (AAF) and N-OH-2-acetylaminofluorene (N-OH AAF) in primary rat hepatocytes isolated from untreated and 3-methylcholanthrene (3-MC) treated rats was investigated. 3-MC treatment was not necessary for the dose-dependent induction of UDS induced by N-OH AAF, suggesting the presence of enzyme levels adequate for its esterification to an active form in isolated primary hepatocytes. Although all doses of AAF increased the level of [3H]thymidine incorporation above that of the control, a dose-dependent response could not be demonstrated, suggesting inadequate constitutive levels of N-hydroxylating enzymes. Treatment of rats with 3-MC 24 h prior to hepatocyte isolation resulted in a dose-dependent induction of UDS by AAF. 3-MC treatment increased the amount of UDS per cell, as well as the percentage of cells induced to repair their DNA.