Effect of pre-conceptional external or internal irradiation of N5 male mice and the risk of leukemia in their offspring

Male mice of the N5 strain were exposed to a unique external X-ray dose of 500 cGy, or to i.p. injections of tritiated water (HTO) over a 30 day period, which resulted in an estimated total internal exposure of 150 cGy. The paternal X-ray irradiation resulted in a marginally significant (P = 0.07) doubling of the leukemia/lymphoma rate in the offspring, over a 1 year observation period. The constitutive gene expression of granulocyte-macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor (TNF) (two cytokines associated with hematopoiesis and immune response) spontaneously diminished between the ages of 6 months and 12 months in the bone marrows and in the spleens of these mice, and paternal X-ray exposure influenced the statistical significance of this diminution. Male exposure to HTO resulted in a statistically significant several-fold increase of leukemia incidence among the young offspring. However this increase tended to diminish as older mice were observed, and was no longer significant at 1 year of age. The overall leukemia incidence in the offspring of the HTO-exposed fathers was significantly dependent on the maturation stage of the sperm-forming cells during the HTO exposure, which suggests an influence of such an exposure.