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Differential Sensitivity of AKR Murine Leukemia and Normal Bone Marrow Cells to Hyperthermia¹

Departments of Human Oncology [H.I.R., R.A.S., P.A.M., K.M.], Anatomy [A. W. C.], and Physiology [W. H. D.], University of Wisconsin Medical School, Madison, Wisconsin 53792

To determine if there is a differential effect of hyperthermia on AKR murine leukemia and AKR normal bone marrow cells incubated in vitro, the fractional survival of leukemic and of normal cells with proliferative potential as a function of heating exposure was estimated by evaluating spleen colony formation. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 centigrays) mice; leukemic colony-forming units were assayed in nonirradiated mice. Electron micrographic studies of leukemic cells treated with 41.8° hyperthermia found that structural damage to the cell, i.e., changes in the Golgi apparatus, was associated with the lack of ability to form colonies. AKR leukemia cells were more sensitive than normal cells to hyperthermic killing at 41.8° and at 42.5°. This differential was found whether cells of each type were heated separately or when mixed together. This model system demonstrates an inherently greater sensitivity of neoplastic cells, as compared to normal syngeneic stem cells, to thermal killing. This finding may have relevance to autologous bone marrow transplantation in humans.

¹ Supported in part by: NIH: RO1-CA24872, R25-CA18397, P30-CA14520, NS-11445; American Cancer Society: IN-35; Madison Leukemia Society; 120164 from University of Wisconsin. Presented in part at the Radiation Research Society, April 17, 1982, Salt Lake City, Utah (13).

² American Cancer Society Junior Faculty Fellow; supported in part by USPHS Grant RO1-CA35361 awarded by the National Cancer Institute, Department of Health and Human Services. To whom requests for reprints should be addressed.

Received 4/11/83. Accepted 7/13/83.

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