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 in preventing carcinogenesis by at least two different mechanisms, by evoking 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 responses 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 lymphoid cells. We used two isogenic cell lines, TK6 harboring wild-type p53, and WI-L2-NS, which carries a mutant p53. A significant difference in sensitivity was observed at 50 microg/ml methyl methane-sulfonate (MMS) between the two cell lines used. In addition, a clear p53-mediated contribution to apoptosis in MMS-induced cell death was observed. However, we did not observe any differences in repair of MMS-lesions, as 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 reflection of differences in strand-break frequency or repair capacity.
Ryu
J C
JC
Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul. ryujc@kist.re.kr
Seo
Y R
YR
Smith
M L
ML
Han
S S
SS
D000478:Alkylation; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects*; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
D009153:Mutagens; D013778:Tetrazolium Salts; D013844:Thiazoles; D008741:Methyl Methanesulfonate; C022616:thiazolyl blue