p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells

摘要: Temozolomide (TMZ) is a DNA-methylating agent that has recently been introduced into Phase II and III trials for the treatment of gliomas. TMZ produces O6-methylguanine in DNA, which mispairs with thymine during next cycle DNA replication. Subsequent futile cycles mismatch repair can lead to p53-associated apoptotic cell death, although this mechanism described mostly hematopoietic neoplasms. We studied action gliomas role p53 might play by using U87 glioma cells were either p53-wild-type or p53-deficient (by virtue expression viral oncoprotein E6). LN-Z308 cells, gene deleted, also used. p53-proficient MG underwent prolonged, p53- p21(Waf1/Cip1)-associated G2-M arrest beginning 2 days after treatment. Although very few these apoptosis, most senescence over 10-day period. (E6-transfected LN-Z308) similarly response TMZ, but was accompanied only minor changes p21(Waf1/Cip1) reversed within 7 association appearance 8n subG1 content. These results suggest respond undergoing arrest. not necessary occur important duration ultimate fate TMZ-treated cells. Therefore, integrity checkpoint may be cytotoxicity