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Effects of Elevated Temperatures and Drugs on the Viability of L1210 Leukemia Cells¹

McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The lethal action of elevated temperatures on neoplastic cells has been determined quantitatively by means of an in vitro-in vivo system of L1210 leukemia cells. Temperatures from 37° to 40° have little effect on these cells. Prolonged exposure at 41° impairs their viability. Between 41° and 42° the lethal effect increases markedly; in Fischer medium, a 4-log kill is achieved at 42° in 3 hr. The exposure of L1210 leukemia cells to a temperature of 42° for a short time sensitizes them to the action of lower temperatures. A 3-hr exposure at 40° has a highly lethal effect when applied after an initial treatment at 42°. If the sequence of heating is reversed, no such effect is observed. Many drugs have been tested for combined therapy. L-erythro-,ß-Dihydroxybutyraldehyde has been found to act synergistically with heat. DL-Glyceraldehyde, L-phenylalanine mustard, actinomycin D, and sodium oxamate are also active in combination with heat. However, if toxicity to humans is considered, only DL-erythro-,ß-dihydroxybutyraldehyde, DL-glyceraldehyde, and phenylalanine mustard can be considered as suitable for clinical trial in combination with heat.

¹ This work was supported in part by Grant CA7175, from the National Cancer Institute, NIH.

² Present address: Stehlin Foundation, 834 Hermann Professional Building, Houston, Texas.

³ American Cancer Society Professor of Oncology.

Received 11/12/69. Accepted 1/26/70.

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