Three major reasons why transgenerational effects of radiation are difficult to detect in humans.

Purpose: Ionizing radiation can induce mutations in germ cells in various organisms, including fruit flies and mice. However, currently, there is no clear evidence for the transgenerational effects of radiation in humans. This review is an effort to identify possible reasons for the lack of such observations.

Methods: Literature search and narrative review.

Results: 1) In both mice and humans, resting oocytes locate primarily in the cortical region of the ovary where the number of blood vessels is very low especially when young and extra-cellular material is rich, and this region is consequently hypoxic, which probably leads to immature oocytes being resistant to the cell killing and mutagenic effects of radiation. 2) In studies of spermatogonia, the mouse genes used for specific locus test (SLT) studies, which include coat color genes, were hypermutable when compared to many other genes. Recent studies which examined over 1000 segments of genomic DNA indicate that the induction rate of deletion mutation per segment was on the order of 10 per Gy, which is one order of magnitude lower than that obtained from the SLT data. Therefore, it appears possible that detecting any transgenerational effects of radiation following human male exposures will be difficult due to a lack of mutable marker genes. 3) Fetal malformations were examined in studies in humans, but the genetic component in such malformations is low, and abnormal fetuses are prone to undergo miscarriage which does not occur in mice, and which leads to difficulties in detecting transgenerational effects.

Conclusion: The lack of clear evidence for radiation effects in humans probably does not result from any problem in the methodologies used but may be due largely to biological properties. Currently, whole genome sequencing studies of exposed parents and offspring are planned, but ethical guidelines need to be followed to avoid discrimination, which had once happened to the atomic bomb survivors.