Human lymphoblastoid cell lines expressing mutant p53 exhibit decreased sensitivity to cisplatin-induced cytotoxicity

grantor: University of TorontoCisplatin is a chemotherapeutic agent commonly used, though with variable results, in treatment of recurrent non-Hodgkin's lymphoma. With the aim of obtaining definite evidence for p53 involvement in cisplatin-dependent apoptosis in human B lymphocytes we have designed an experimental system where human lymphoblastoid cells were transfected with expression vectors containing p53 cDNA mutated at either codon 135 or 246. The cells were subjected to cisplatin treatment or $\gamma$-radiation and observed for changes in cell cycle arrest and apoptosis. Results suggest a role for p53 in cisplatin induced cytotoxicity. In addition increases in the level of mutant p53 RNA after irradiation or cisplatin treatment suggest that these agents may not only stabilize wild type p53 protein but also induce or stabilize mutant p53 RNA. Finally results indicate that both irradiation and cisplatin should be used with caution in the treatment of lymphoid tumours bearing mutations of p53. (Abstract shortened by UMI.)M.Sc