EFFECT OF PRECONCEPTIONAL 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 dos e 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 sign ificant (P = 0.07) doubling of the leukemia/lymphoma rate in the offsp ring, over a 1 year observation period. The constitutive gene expressi on of granulocyte-macrophage colony stimulating factor (GM-CSF) and tu mour necrosis factor (TNF) (two cytokines associated with hematopoiesi s and immune response) spontaneously diminished between the ages of 6 months and 12 months in the bone marrows and in the spleens of these m ice, and paternal X-ray exposure influenced the statistical significan ce of this diminution, Male exposure to HTO resulted in a statisticall y significant several-fold increase of leukemia incidence among the yo ung offspring. However this increase tended to diminish as older mice were observed, and was no longer significant at 1 year of age. The ove rall leukemia incidence in the offspring of the HTO-exposed fathers wa s significantly dependent on the maturation stage of the sperm-forming cells during the HTO exposure, which suggests an influence of such an exposure.