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

Abstract

The interaction between the cytotoxic effect of bleomycin (BLM) or cis-diamminedichloroplatinum(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 degrees 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 degrees C was minimal when cis-DDP at 43 degrees 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 degrees C; and (c) pre-heating decreased the magnitude of thermal sensitization 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.

Effects of combined treatment of chemotherapeutics and hyperthermia on survival and the regulation of heat shock proteins in dunning R3327 prostate carcinoma cells

“…3) but not for cisplatin or 5-fluorouracil. Similar results showing no desensitizing effect of thermotolerance to cisplatin-related cytotoxicity were also reported by Majima et al [30].…”

Cisplatin sensitivity and thermochemosensitisation in thermotolerant cDDP-sensitive and -resistant cell lines

“…Since the cDDP sensitivity of the cells is equal to the sensitivity of control cells at this time point, the state of thermotolerance does not seem to confer resistance against cDDP toxicity to the cells. Unaltered cDDP sensitivity at 37'C in thermotolerant cells is in accordance with previously published data of both in vitro (Neilan et al, 1986;Miller et al, 1989;Majima et al, 1992) and in vivo (Yano et al, 1993) studies. Also, absence of interaction of thermotolerance with the cytotoxicity of several other drugs was observed, e.g.…”

“…Also, absence of interaction of thermotolerance with the cytotoxicity of several other drugs was observed, e.g. bleomycin toxicity has been shown to be unaltered in thermotolerant cells in a number of studies (Morgan et al, 1979;Neilan et al, 1986;Majima et al, 1992 (Morgan et al, 1979;Herman et al, 1982;Neilan et al, 1986;Majima et al, 1992 Burgman and Konings, 1992). This leads to, among other things, an increase in the protein mass of nuclei isolated from heated cells (Roti-Roti and Wimward, 1978).…”

In vitro Effect of Hyperthermia on Chemoenhancement and Uptake of Cisplatin in Human Pharyngeal Carcinoma KB Cells

“…The synergistic interaction between hyperthermia and chemotherapeutic agents is usually greatest when they are simultaneously applied, and it gradually decreases as the interval between the two increases. In animal tumors, this synergism is greater for most agents when the drug is given immediately before rather than immediately after hyper thermia [7,8], An exception is CDDP which has a strong synergistic effect when applied immediately before or immediately after hy perthermia in vitro [9], On the other hand, Majima et al [26] have reported that preheat ing of CHO cells enhanced CDDP cytotoxici ty when the drug was given shortly after heat ing, whereas pretreatment by CDDP did not alter the sensitivity to subsequent hyperther mia. However, the effects of temperature and sequence on the interaction between CDDP and hyperthermia have not been fully ad dressed.…”