DNA EXCISION-REPAIR SYNTHESIS IS ENHANCED IN A MURINE LEUKEMIA-L1210 CELL-LINE RESISTANT TO CISPLATIN

Among various molecular mechanisms of cell resistance to antitumor agents such as cisplatin, it has recently been suggested that enhanced DNA-repair activity might be involved in the resistant phenotype of cell lines. Mouse leukemia-cisplatin-resistant cell lines L1210/10 (adapted in vitro) and L1210/DDP (adapted in vivo) have been reported to exhibit an increase DNA-repair activity, as determined by host-cell reactivation after transformation with damaged plasmids. In this paper, excision-repair activity was monitored by an in-vitro assay allowing quantification of DNA-repair synthesis in cell extracts from resistant and sensitive parental cells (L1210/10 versus L1210/0 and L1210/DDP versus L1210/S). Experimental conditions for optimal repair-synthesis activity were found to be different from these reported with human cell-line extracts. L1210/S sensitive cell line, grown in vivo by a weekly intraperitoneal graft in mice, displayed a repair activity about fourfold lower than the same cell line maintained in vitro or than L1210/0 cell grown in vitro. The repair activity was found similar in a L1210/10 and L1210/0 cell lines. but it was enhanced in L1210/DDP resistant cell line when compared with its parental line.