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A Delayed Cytotoxic Reaction for 6-Mercaptopurine¹

University of Alberta Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada

In this study of the cytotoxic action of 6-mercaptopurine (6MP), a delay was demonstrated between exposure of mouse tumor cells to 6MP and physical manifestations of toxicity by the cells. Proliferation of cells of the Ehrlich ascites carcinoma in vivo and of mouse lymphoma L5178Y in culture continued during and beyond the period of exposure to 6MP, although this treatment was ultimately lethal. In the case of the cultured lymphoma cells, the terminal phase of postexposure proliferation was characterized by unbalanced growth in which cell protein and size increased above normal values. Subsequently, division ceased and the enlarged cells disintegrated. Two effects of 6MP were distinguishable in cultures of the lymphoma cells, the delayed cytotoxic activity and an acute inhibitory effect on the rate of cell proliferation.

¹ Supported by the National Cancer Institute of Canada and the Medical Research Council of Canada.

² Research Fellow of the National Cancer Institute of Canada.

³ Present address: Slovak Polytechnical Institute, Bratislava, Czechoslovakia.

⁴ Present address: Cancer Institute (Japanese Foundation for Cancer Research), Nishi-Sugamo, Toshima-ku, Tokyo, Japan.

Received 11/16/70. Accepted 10/21/71.