Protection against cis-Diamminedichloroplatinum Cytotoxicity and Mutagenicity in V79 Cells by 2-[(Aminopropyl)amino]ethanethiol

摘要: The effect(s) of the radioprotector 2-[(aminopropyl)amino]ethanethiol (WR1065) on cis-diamminedichloroplatinum(II) (cis-DDP)-induced cytotoxicity and mutagenesis at hypoxanthineguanine phosphoribosyl transferase locus in V79 Chinese hamster cells was examined. With a standard exposure time 30 min for both agents, WR1065, final working concentration 4mM, added to either prior to, during, or immediately following treatment with selected doses cis-DDP. respect cell survival, dose modification factors 2.9, 1.4, 1.4 were obtained treated under each these conditions, respectively. induction mutants all conditions linear as function cis-DDP concentration. Mutation frequencies per microgram 25 X 10(-7), 1 5 11 10(-7) protocols involving no protector present WR1065 before, after treatment, No WR1065-mediated derived from wild-type mutant colonies observed. These data demonstrate that free thiol S-2-(3-amino-propylamino)ethyl phosphorothioic acid (WR2721) which is currently being evaluated clinical trials, affords substantial protection against cytotoxic mutagenic effects cis-DDP, most effective occurring when administered treatment. Due their ability better protect normal compared tumor tissue acute effects, protectors have generated considerable interest use improving therapeutic gain radiation therapy chemotherapy. compounds also agents may be an important additional benefit consideration human neoplasia.