Interaction between the kinetics of thermotolerance and effect of cis-diamminedichloroplatinum(II) or bleomycin given at 37 or 43°C

Abstract

The interaction between the cytotoxic effect of bleomycin (BLM) or cis-diammine-dichloroplatinum(II) (cis-DDP) and the kinetics of thermotolerance was studied in cultured Chinese hamster ovary (CHO) cells. Pre-heated cells were treated with cis-DDP or BLM at 37 or 43°C for various times after heating. Pre-heating enhanced cis-DDP cytotoxicity given immediately after heating, but this enhancement decreased within 24 h to an additive level. Cell survival following the initial heating and the second treatment of ‘cis-DDP at 43°C’ was minimal when cis-DDP at 43°C was given immediately after the initial heating, but became higher with increasing treatment interval and reached ‘less than additive’ level when the treatment interval was extended to more than 24 h. This alteration in cell survival appeared to follow the kinetics of thermotolerance. The interaction between BLM treatment and the kinetics of thermotolerance was similar to that of cis-DDP. However, pre-heating enhanced BLM cytotoxicity much less extensively than cis-DDP cytotoxicity. These results indicate that: (a) pre-heating of cells enhanced drug-toxicity when the drug was given shortly after heating, but the magnitude of this enhancement depended on the drug; (b) pre-heating did not influence the cytotoxicity of drugs given at 37°C; and (c) pre-heating decreased the magnitude of thermal sensizitation of drug cytotoxicity. The magnitude of the decrease in thermal sensitization appeared to be parallel to the kinetics of thermotolerance. In this study it was also demonstrated that pre-treatment of CHO cells by cis-DDP or BLM did not alter sensitivity to subsequent drug treatment, hyperthermia or thermochemotherapy.

Key Words:

• Cis-diamminedichloroplatinum(II)
• bleomycin
• thermochemotherapy
• thermotolerance
• thermal enhancement
• CHO cells