COMBINED EFFECT OF TRANS-DIAMMINEDICHLOROPLATINUM(II) AND HYPERTHERMIA ON MURINE AND HUMAN-TUMOR CELLS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (12) , 6232-6237
Abstract
Trans-Diamminedichloroplatinum(II), a paradigm of an inactive platinum compound, exhibited cytotoxic effect against HEP-2 human tumor cells, TA3Ha murine tumor cells, and freshly collected human ovarian carcinoma cells when combined with hyperthermia (43.degree. , 30 min). The heat treatment reduced the Do of trans-platinum from 56 to 16.5 .mu.g/ml in the HEP-2 system and from an undeterminable value at 37.degree. to 8.2 .mu.g/ml in the TA3Ha system. Heat treatment before trans-platinum was more cytotoxic than that after trans-platinum in the TA3Ha system (P < 0.001). TA3Ha cells treated in vitro with 40 .mu.g/ml TDDP at 43.degree. failed to form tumors in mice upon subcutaneous implatation into the tails of mice. In contrast, these agents given singly did not alter the tumor-forming ability to TA3Ha cells. In vivo administration of trans-platinum after hyperthermia (43.degree. for 30 min) retarded the growth of TA3Ha tumors compared to either treatment alone. trans-Platinum did not form detectable DNA-interstrand cross-links in the HEP-2 cells treated at 37.degree. or 43.degree.. However, the DNA-protein cross-links were detectable under these conditions. The frequencies of DNA-protein cross-links were higher in the cells treated at 43.degree. than in those treated at 37.degree., both immedately after and 12 h after the treatment with trans-platinum. Heat alone did not induce the formation of either DNA-interstand or DNA-protein cross-links. Heat treatment did not appear to enhance the entry of trans-platinum into the cells.