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Interactions between Hyperthermia and Irradiation in Two Human Lymphoblastic Leukemia Cell Lines in Vitro¹

Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792 [J. D. C., H. I. R., R. T. M., J. J. G.], and Department of Microbiology-Immunology and the Cancer Center of Northwestern University Medical School, Chicago, Illinois 60611 [N. B.]

Thermal radiosensitization was studied in two human T-cell acute lymphoblastic leukemia cell lines (JM and MOLT3) with regard to heat-irradiation sequence and heating duration.

In MOLT3 thermal radiosensitization was maximal when 43.5°C hyperthermia immediately preceded or followed irradiation; at 41.5°C, radiosensitization was maximal with hyperthermia immediately before or up to 3 h after irradiation. In JM, enhancement of radiation killing was unexpectedly maximal when 41.5 or 43.5°C hyperthermia preceded irradiation by 2 to 4 h.

Thermal radiosensitization increased exponentially with increasing duration of heating at 41.5°C for at least 3 h in MOLT3. In contrast, in JM, radiosensitization increased exponentially for 1.6 h but additional heating (up to 3 h net heating) had no appreciable further effect on radiation killing.

For JM, repair of single and double stranded DNA breaks was investigated using alkaline and neutral elution techniques to determine whether the unusual results regarding heat-irradiation sequencing were related to effects of heat on repair of DNA damage. These studies were unable to detect significant differences in repair of single or double stranded DNA breaks between unheated control cells and cells heated at 41.5°C for 1 h ending 4 h before irradiation. The direct cytotoxicity of hyperthermia was also studied in both cell lines.

¹ Supported by Midwest Athletes Against Childhood Cancer and in part by RO1-CA-27306, RO1-CA-35361.

² American Cancer Society Clinical Oncology Fellow.

³ American Cancer Society Faculty Fellow. To whom requests for reprints should be addressed.

Received 12/ 8/87. Revised 3/14/88. Accepted 3/31/88.