Maternal effects and cancer risk in the progeny of mice exposed to X-rays before conception

To investigate in an animal model whether preconceptual X-ray exposure leads to an altered tumor rate and spectrum in the offspring, a transgeneration carcinogenesis study was carried out. Female mice received X-ray irradiation (2×2 Gray) 2 weeks prior to mating with untreated males. After weaning, half of the descendants were exposed for 6 months to the immunomodulating and tumor-promoting compound cyclosporine A (CsA) by diet, the others remained untreated. The animals were maintained for their entire lifespan, terminal sacrifices were carried out after 28 months. Complete autopsy was performed, and three protocol organs (lung, liver and spleen) were examined histologically, together with any suspicious lesions in other organs. Fertility and the lifetime of the maternal mice were reduced by the X-ray irradiation, and their incidence of lung and liver tumors was increased as compared to non-irradiated mice. The descendants of all groups revealed comparable body weights and mortality rates. The incidence of hematopoietic/lymphoreticular tissue tumors increased in the female hybrids by 6 months of CsA-treatment. A higher incidence of lung and liver tumors in the sham-treated male progeny of irradiated mothers was detected, pointing to a possible germ cell-transmitted alteration initiated by the preconceptual maternal X-ray exposure.