Challenges for Future Study of the Late Effects of Therapeutic Radiation in Cancer Survivors and Also Their Progeny

There is an increasing concern to understand the mechanism for the late effects of radiation exposure, not only to the individual exposed but also to family members and progeny. Ionizing irradiation is known to produce infertility by elimination of oocytes and spermatogonia. Nonlethal effects on the reproductive system have also been documented in animal models and include genetic defects in the progeny of exposed individuals, which arise from radiation-induced changes in germ cells. Fetal irradiation in early gestation in animal models is associated with lethality; however, low radiation doses and exposure during second and third trimester of pregnancy in humans lead to nonlethal effects including hydrocephalus, vascular and cardiac abnormalities, and other abnormalities associated with damage to developing organs. Transmission of genetic defects to progeny has now been demonstrated with animal models. Of particular interest has been the demonstration of epigenetic effects of radiation. Now, there is the additional need to define the effects of radiation countermeasures that would be delivered to exposed individuals, which might lead to subsequent induction of changes in their progeny. Research in this area is now a major focus in radiobiology.