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The Use of X-Ray and Nitrogen Mustard To Determine the Mitotic and Intermitotic Times in Normal and Malignant Rat Tissues^*

William R. Widner, John B. Storer and C. C. Lushbaugh

( Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico)

1. By determining the rate of decline of the mitotic indices of the jejunum, bone marrow, Jensen sarcoma, and Walker rat carcinoma 256 of rats immediately following exposure to x-radiation, it was found possible to determine the length of time spent by the cells in mitosis and in the resting stage. Comparison of the results of this experiment with those of others revealed a close agreement between the mitotic times for a wide variety of tissues, derived by serveral different methods.

2. From these data it would appear that the time required for any cell of the rat to produce two daughter cells following breakdown of the nuclear membrane in early prophase is constant and measures approximately 25.4 minutes. It would also appear that the mitotic index of a tissue is dependent upon the length of the interphase or resting stage and that changes in rate of cellular proliferation are the result of changes in the length of the resting stage.

3. It was not found possible to substitute nitrogen mustard for x-radiation as a means of producing mitotic arrest in this method of determining mitotic time, because nitrogen mustard apparently causes an early premitotic arrest as well as an arrest in early prophase, while also having a colchicine-like effect later in mitosis. These differences in mode of action of nitrogen mustard upon cell division lead to unduly prolonged mitotic times as derived by this method.

^* Work done under the auspices of the AEC.

This paper is part of a thesis submitted to the University of New Mexico in partial fulfillment of the requirements for the Ph.D. degree.

Received 8/ 7/51.