Causes of death and their contribution to radiation-induced life shortening in intact and ovariectomized mice

Shortening of mean life span and tumor incidence were investigated in intact or ovariectomized BALB/c and RFM female mice exposed to γ irradiation. In the intact mice, radiation-induced life shortening was considerably greater than in the ovariectomized mice. Both a 'dose-independent' and a 'dose-dependent' component of life-shortening injury were demonstrated in the intact animals. Ovariectomy abolished the dose-independent component. Classes of tumors were categorized as lethal or incidental on the basis of prevalence in randomly sacrificed and moribund animals. Once this classification was made, the corrected incidence of disease categories was estimated and the relative risk of death as a function of dose was calculated for each class of diseases. The dose-independent life shortening in intact mice was due solely to nonneoplastic causes of death. In both strains, the dose-dependent component of life shortening (the only one present in ovariectomized animals) was due entirely to lethal neoplasms. In the RFM mice, the overwhelming cause of death from neoplasms was from tumors of the reticular tissues. In the BALB/c strain, reticular tissue tumors and lethal solid tumors contributed about equally. Ovariectomized animals were more resistant to radiation-induced tumors. These findings support the conclusion that host factors play a major role in the expression of tumors and the conclusion of other authors that radiation-induced life shortening (except of intact female mice of some strains) is due primarily to the induction of lethal neoplasms.