RATE OF HEATING AS A DETERMINANT OF HYPERTHERMIC CYTO-TOXICITY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (9) , 3519-3523
Abstract
In Chinese hamster ovary [CHO] cells and in normal [Rat-1] and transformed [Rat-1 (wt/RSV)] rat embryonic fibroblasts, survival as a function of time at 42.4.degree. C was dependent upon the rate of heating from 37.degree. C to 42.4.degree. C. Unexpectedly, the untransformed rat fibroblasts were more heat sensitive than were the transformed cells, and the protective effect of slow rates of heating upon survival at 42.4.degree. C was also more pronounced in the normal cells than in the transformed cells. In CHO cells, total cellular cholesterol content and cell volume changed significantly with time at 42.4.degree. C when cells were heated immediately (37-42.4.degree. C within 3 min) but did not vary significantly during 6 h at 42.4.degree. C in cells heated from 37 to 42.4.degree. C over 3 h. CHO cells heated immediately to 42.4.degree. C also showed a significant drop in the protein content of the particulate fraction with time at 42.4.degree. C. In contrast, cells heated over 3 h showed a significant increase in the protein content of the particulate fraction with time at 42.4.degree. C. If cells are heated to hyperthermic temperatures over sufficiently long intervals, mechanisms may have time to develop which protect the cell membrane against changes associated with cell death in rapidly heated cells. The protective effect of slow rates of heating may partially explain the relative lack of success thus far observed with the use of whole-body hyperthermia [an antitumor modality] in which heating from 37.degree. C to 42.degree. C often requires 2-3 h.