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The Effects of Nitrogen Mustard and Dimethyl Myleran on Murine Leukemia Cell Lines of Different Radiosensitivity in Vitro¹

Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W.3, England

The effects of nitrogen mustard and dimethyl myleran on 3 mutants of murine leukemia L5178Y—"radioresistant" and "radiosensitive" diploid cell lines and a tetraploid line—have been studied. A close parallelism was found in the response of "radioresistant" and "radiosensitive" cells to treatment with nitrogen mustard, dimethyl myleran, and X-radiation; in each case the D_o for the "radioresistant" line was twice that of the "radiosensitive" cell line. The tetraploid cell line showed marked differences in response to the 3 agents: it showed increased resistance to nitrogen mustard, increased sensitivity to dimethyl myleran, and no change in response to X-radiation, all relative to the response of the "radioresistant" diploid cell line to these same agents.

The effect of dimethyl myleran more closely resembled that of X-radiation in that cell division continued for some time after treatment and storage at suboptimal temperature facilitated post-treatment recovery processes.

The monofunctional mustard, dimethyl chloroethylamine, was approximately 35 times less potent in its cytocidal effect than nitrogen mustard.

The cyclic ethyleneimmonium ion of nitrogen mustard appeared to retain the full cytocidal action of nitrogen mustard in this system.

Attempts to induce mutants of L5178Y more resistant to nitrogen mustard and dimethyl myleran by repeated treatment of surviving cells were unsuccessful.

¹ This work was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research, Royal Cancer Hospital) from the Medical Research Council, the British Empire Cancer Campaign, the Anna Fuller Fund, and the National Cancer Institute of the USPHS.

² Canadian Hadassah Cancer Research Fellow, National Cancer Institute of Canada. Present address: Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.

Received 2/22/65.