THERMAL ENHANCEMENT OF DNA DAMAGE IN MAMMALIAN-CELLS TREATED WITH CIS-DIAMMINEDICHLOROPLATINUM(II)

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (4) , 1136-1139
Abstract
The cytotoxic effects of cis-diamminedichloropatinum(II) (cis-DDP) were strongly potentiated by hyperthermia. The molecular mechanisms responsible for this potentiation were investigated by assaying the degree of DNA cross-linking produced under the different drug treatment conditions by the technique of alkaline elution. The [hamster ovary CHO] cells treated with the drug at 43.degree. C had a greater amount of DNA cross-linking immediately after treatment than did cells treated with the drug at 37.degree. C indicating a possible thermal enhancement of drug uptake by the cells. Whereas the hyperthermia potentiated the cytotoxicity of cis-DDP by a factor of nearly 10, the degree of DNA cross-linking was only enhanced by a factor of 6.5, suggesting that while a large portion of the enhanced cytotoxicity may be attributed to the increased cross-linking other factors may also play some role. The possible influence of hyperthermia on the repair of the DNA damage induced by cis-DDP was investigated; however, no significant difference in the rate of disappearance of cross-links between cells treated at 37 or 43.degree. C was observed. Advantageous combination of chemotherapy with cis-DDP and hyperthermia for the treatment of cancer is implied by these results.