Transgenerational effects of preconception paternal contamination with Fe-55

The conjecture that germline mutations induced by radiation exposure before conception may predispose subsequent offspring to cancer remains contentio us. Previous experimental studies have shown that preconception paternal ir radiation with Pu-239 induces perturbations in the hemopoietic systems of o ffspring and influences sensitivity to a secondary carcinogen. In the prese nt study, male DBA2 mice were injected intravenously with the Auger electro n emitter Fe-55 (4 kBq g(-1)) 18 or 84 days before mating with normal femal es. Comet analysis showed an increased incidence of DNA strand breaks in sp erm from contaminated animals after 84 days, but not after 18 days, indicat ing spermatogonial rather than spermatid damage. Offspring were either assa yed for changes in bone marrow stem cells and committed progenitors or chal lenged with the chemical carcinogen methyl nitrosourea (MNU, 50 mg/kg) at 1 0 weeks of age and monitored for the onset of malignancy. Offspring from ir radiated fathers had normal peripheral blood profiles, although the stem ce ll population was amplified in offspring arising from those exposed to Fe-5 5 at 84 days before conception. Exposure to MNU significantly increased the incidence of lympho-hemopoietic malignancies in offspring from the 84-day group, but not in those from the 18-day group. These findings support the h ypothesis that aberrations that are potentially leukemogenic may be transmi tted to offspring after radiation damage to the paternal germline. (C) 2001 by Radiation Research Society.