Severity of organ injury as a predictor of acute mortality for disparate patterns of absorbed dose distribution.

Nonuniform distribution of absorbed dose is frequently encountered in the irradiated mammal; the degree of nonuniform distribution is generally more severe as the size of the animal increases and the energy or penetrating power of the radiation decreases. However, acute mortality under these conditions, e.g., from the hematopoietic syndrome, appears not to be consistently predictable from the dose at any given location or locations within the animal. It is thus reasonable to seek a biological quantity that may be adequate for this purpose. Accordingly, it was postulated that, in animals dying from the bone marrow syndrome, survival is determined by the total number of viable stem cells remaining in the entire body, independent of their distribution. To test this hypothesis, the LD50/30 value for mice exposed to nonuniform irradiation of varying degrees of severity was obtained, as was that for mice receiving uniform total-body irradiation. The distribution of bone marrow in transverse segments of tissue along the spinal axis was determined, as was the dose to each of the segments. The data were analyzed by multiplying, for each segment, the fraction of stem cells in the fraction of cells surviving, as determined from the dose and a survival curve for stem cells determined separately. The sum of these products yielded the surviving number of stem cells in the total mouse, for both the uniformly and nonuniformly exposed animals. The surviving fraction was found to differ by no more than 20%; this was taken to be reasonable evidence that, based on the number of surviving stem cells, it is possible to predict the mortality rate for both uniform and markedly nonuniform irradiation.