A mortality determinant in nonuniform exposures of the mammal.

Abstract

It is widely accepted that survival in most mammals exposed uniformly to penetrating radiation in the LD50(30) (hematological syndrome) range depends primarily on maintenance of a critical level of neutrophils and platelets in the peripheral blood. This minimum level depends in turn on the survival or proliferative integrity of a critical number or fraction of the stem cells in the total active bone marrow mass (1). From dose-survival curves established for bone marrow stem cells in the mammal (2-4), it appears that the dose-effect curve is closely approximated by an exponential function over a range of exposures that more than spans the LD50(30) range. It is reasonable to assume that subunits of the total marrow mass have the same number of stem cells per unit mass, and that the stem cells of each subunit, considered independently, are subject to the same exponential dose-effect relationship as that for the total marrow. It is further reasonable to assume that a surviving stem cell will, after irradiation, contribute mature cells to the peripheral blood at a rate that is independent of its location in the marrow. The foregoing statements form a logical basis for a stem cell model for survival; that is, survival of the animal depends on the same critical surviving fraction of stem cells, whether following uniform or nonuniform exposure. This fraction can be calculated from values for (1) the relative amounts of active bone marrow (stem cells) in different parts of the body; (2) the doses to these parts; and (3) the dosesurvival curve for stem cells.