Species differences in the time-dependent induction of unscheduled DNA synthesis in primary hepatocytes

The detectability of quantitative species differences in the in vitro hepatocyte DNA repair assay (UDS test) was shown to be strongly dependent on the duration of treatment. Primary hepatocytes of rats and Chinese hamsters were treated for 2 and 18 hr with aflatoxin B(1) (AFB(1)) or 2-acetylaminofluorene (2-AAF). After 18 hr of treatment with either compound the DNA repair response was much stronger in rat hepatocytes than in hamster hepatocytes, whereas after 2 hr of treatment the hepatocytes of the two species showed similar responses. Experiments with the direct-acting mutagen methylmethane sulfonate indicated that the hepatocytes of both species exhibit similar capacities for DNA repair. Since the rates of metabolism of AFB(1)- and 2-AAF also did not show significant differences between the species, the observed 2 hr/18 hr discrepancy must be attributed to different DNA repair kinetics. Further experiments showed that in comparison with rat hepatocytes, hamster hepatocytes recovered more rapidly from the isolation procedure, but their DNA-repair activity decreased more rapidly during the first hours of treatment. Such fundamental differences have to be taken into account when comparing the results of UDS tests that have been carried out with hepatocytes from different species.