Human peripheral blood mononuclear cells from normal healthy volunteers were exposed to elevated temperatures of 41–43° for up to 6 hr. Thereafter, the cells were stimulated with phytohemagglutinin in vitro in order to measure indirectly the surviving fraction. DNA replication in heated cells in response to phytohemagglutinin was found to be a sensitive indicator of thermal injury. Exposure to even 40° for 2 hr lowered thymidine incorporation at early time points after phytohemagglutinin stimulation, but the cells were able to recover from thermal injury after exposure for up to 4 hr at 42°. At 43°, exposure for even 1 to 2 hr caused irreversible damage. The changes in thymidine incorporation were not due to changes in endogenous nucleotide pools since parallel changes were observed in DNA polymerase activity. Thus, the heat sensitivity of normal human lymphocytes could be a limiting factor for use of hyperthermia as an adjunct to radiotherapy and chemotherapy of human cancer.


This work was supported by USPHS Grants CA-11524, CA-12818, and CA-06551 from the NIH; the Internal Cancer Research Data Bank Program of the National Cancer Institute; the NIH (US) under Contract No. 1-CO-65341 (International Cancer Research Technology Transfer-ICRETT) with the International Union Against Cancer, and a grant from the Indian National Science Academy. The paper that has appeared previously (3) is designated as Paper 1; Paper 2 is Ref. 23. This paper shall be designated as Paper 3 in the series.

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