The effect of methyl methanesulfonate (MMS)-induced excision repair on p53-dependent apoptosis in human lymphoid cells

The tumor suppressor p53 product has been shown to play an important role i n preventing carcinogenesis by at least two different mechanisms, by evokin g cell cycle arrest and eliciting DNA repair on one hand, or by eliminating damaged cells by induction of apoptosis on the other hand. As a first step toward understanding the relationship between protective re sponses and apoptosis after genotoxic stress, we examined the effect of DNA strand breaks generated from repair processes in respect to acute cellular responses against DNA damage, and on p53-dependent apoptosis in human lymp hoid cells. We used two isogenic cell lines, TK6 harboring wild-type p53, a nd WI-L2-NS, which carries a mutant p53. A significant difference in sensitivity was observed at 50 mug/ml methyl me thanesulfonate (MMS) between the two cell lines used. In addition, a clear p53-mediated contribution to apoptosis in MMS-induced cell death was observ ed. However, we did not observe any differences in repair of MMS-lesions, a s determined by comet assay, between the two cell lines. These data suggest that the differences in apoptosis induction in the two lines are not a ref lection of differences in strand-break frequency or repair capacity.