| Co-Investigator(Kenkyū-buntansha) |
MAJIMA Hideyuki Nihon University, Department of Radiology, Assistant Professor., 歯学部, 講師 (60165701)
WAKAMATSU Yoshiko Nihon University, Department of Pharmacology, Associate Professor., 歯学部, 助教授 (30059084)
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| Research Abstract |
The interaction between the cytotoxic effect of bleomycin (BLM) or cisdiamminedichloroplatinum (II) (cis-DDP) and the kinetics of thermotolerance was studied in cultured Chinese ovary (CHO) cells. The cells were cultured in McCoy's 5a medium supplemented with calf serum, fetal calf serum and antibiotics. All treatments were given by immersing culture flasks into a water bath where a given temperature <plus-minus>0.05^ﾟC was maintained by a heater circulator. Following 10 to 14 days incubation, colonies were stained and counted, and surviving fraction was calculated.
Preheated cells were treated with cis-DDP or BLM at 37 or 43^ﾟC various times after heating. Preheating enhanced cis-DDP cytotoxicity given immediately after heating, but this enhancement disappeared in 24 hours and reached and additive level thereafter. Cell survival following initial heating and the second treatment of cis-DDP treated at 43^ﾟC was minimal when cis-DDP at 43^ﾟC was given immediately after initial heating, b
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ut became higher with increasing treatment interval and reached "less than additive" level when the treatment interval was extended more than 24 hours.This increase and decrease in cell survival appeared to have followed the kinetics of thermotolerance. The interaction between BLM treatment and the kinetics of thermotolerance was similar to that for cis-DDP. However, the enhancement of BLM cytotoxicity by preheating was much less extensive compared to that of cis-DDP cytotoxicity. These results indicated that preheating of cells enhanced the drug-toxicity when the interval between two treatments was short, but the magnitude of this enhancement depended on the drug. This enhancement disappeared within 6 to 24 hours and reached additive level,i. e., the preheating might not protect the cytotoxicity of drugs given at 37^ﾟC. However, preheating decreased the magnitude of thermal sensitization of drug cytotoxicity. The magnitude of this decrease appeared to be parallel to the kinetics of thermo-tolerance. This study also demonstrates that pretreatment CHO cells by cis-DDP or BLM does not alter the sensitivity to subsequent drug treatment, hyperthermia or thermochemotherapy. Less
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