Transgenerational effects of radiation on cancer and other disorders in mice and humans

Abstract

Parental exposure of mice to radiation and chemicals causes a variety of adverse effects in the progeny, and the tumor-susceptibility phenotype is transmissible beyond the first postradiation generation. The induced rates of tumors were 100-fold higher than those known for mouse specific locus mutations. There were clear strain differences in the types of naturally-occurring and induced tumors and most of the latter were malignant. Another important finding was that germ-line exposure elicited very weak tumorigenic responses, but caused persistent hypersensitivity in the offspring for the subsequent development of cancer by the postnatal environment. Various disorders were induced in the offspring of mice exposed to radiation. Microsatellite mutations increase dose-dependently and accumulated for 58 generations in the offspring of male parental mice exposed to single dose of X-rays. Changes in gene expression also transmitted to further generations. Radiation-induced genomic instability in germ cells may enhance cancer and other disorders in next generation. In humans, a higher risk of leukemia and birth defects has been reported in the children of fathers who had been exposed to radionuclides in the nuclear reprocessing plants and to diagnostic radiation. These findings have not been supported in the children of atomic bomb survivors in Hiroshima and Nagasaki, who were exposed to higher doses of atomic radiation. However, long-term monitoring of children by Russian Federation Children's Center of Antiradiation Protection after Chernobyl accident shows higher prevalence of malignant neoplasm, mostly childhood cancer, malformation, and other disorders in the children of residents exposed to contaminated radionuclides (>556 kBq/m2). Persistent accumulation of genomic instability may cause various disorders in a further generation in human. This view will gain support from our mouse experiments, because the induced rate of solid tumors in the offspring of mice exposed to radiation is much higher than that of leukemia.