The kinetics of in vivo sister chromatid exchange induction in mouse bone marrow cells by ethylnitrosourea and methylnitrosourea.

Administration of ethylnitrosourea (ENU) (20, 25, 40, 50, and 60 mg/kg body weight) or methylnitrosourea (MNU) (25, 40, 50, 60, 75, and 80 mg/kg body weight) to male CD-1 mice 2 hr after sc implantation of a 5-bromo-2'-deoxyuridine (BrdUrd) pellet (55 mg) resulted in a dose-dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Treatment with ENU (50 mg/kg body weight) at several time points prior to BrdUrd implantation resulted in a multiphasic curve of SCE induction indicating at least two events that result in SCEs. Treatment with ENU at the time of BrdUrd implantation and post-BrdUrd reflected a similar mechanism apparent in the pre-BrdUrd curve. Treatment with MNU (50 mg/kg body weight) pre- and post-BrdUrd resulted in a linear monophasic curve of SCE induction in both the pre- and post-BrdUrd time periods. The overall MNU time-course curve resembled an inverted V function suggesting the mechanisms of SCE induction for ENU and MNU are different. These observations suggest that at least one explanation for the differences in the time courses for ENU and MNU SCE induction may result from a more persistent lesion being induced by ENU. In addition, these results indicate that in vivo SCE protocols which utilize a single acute chemical exposure at or near the time of BrdUrd labeling may not be useful for judging the relative activities of genotoxic agents.