Cellular Aspects of the Mammalian Radiation Syndrome: II. Cell Depletion in Bone Marrow, Spleen, and Thymus of Young Mice

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Abstract
Quantitative studies of the time course of nucleated cell depletion in the spleen and thymus of young Swiss mice after total-body [gamma]-irradiation have been carried out. These organs resemble the bone marrow in showing no measurable depletion after doses below 50 rads, and then a depletion rate increasing with dose until a dose of 200 to 300 rads has been achieved, after which further increase of dose has no effect up to 1500 rads. The limiting cell depletion rates of these 2 organs are greater than that of the bone marrow, although they are achieved at the same limiting dose of irradiation. These results support the theory that the cells of all 3 tissues have similar single-cell survival curves with respect to reproductive inhibition, and that the principal action during the first 45 hours after irradiation is the suppression of normal reproduction without any appreciable action on the rate of cell destruction or removal from these tissues for the dose range studied. This theory of reproductive inhibition correctly predicted the following experimental results (1) Cell depletion of irradiated bone marrow, thymus, and spleen during the first 40 hours follows the same course in each case, regardless of whether the total body was irradiated or only the part containing the sampled tissue. (2) When massive amounts of vinblastine, a cellular mitotic inhibitor, were administered to mice, the same rate of cell depletion in the bone marrow was achieved as occurs after X-irradiation with doses equal to or beyond the limiting dose. More than 95% of the nucleated cells of the spleen and thymus exhibit the same depletion rate after irradiation with doses at or beyond the limiting value. The discussion has considered: the usefulness of quantitative depletion curves for studying the normal turnover times of cells in different tissues; investigation of differences in turnover times of specific tissues in animals of differing genetic constitution; the study of the mechanism of action of drugs and other chemical, physical, or biological agents in mammals; and determination of the radiation sensitivity of cell reproduction in various tissues in vivo. The normal depletion time for the averaged, nucleated cell population in the bone marrow, spleen, and thymus of normal Swiss mice, 3 to 5 weeks old, has been estimated as 10.6 [plus or minus] 2.5, 6.5 [plus or minus] 1.5, and 4.9 [plus or minus] 1.0 hours, respectively.

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