Transgenerational Genomic Instability due to Preconception Paternal Irradiation?

摘要

Two recent reports described enhanced methyl nitrosourea (MNU) and radiation-induced leukaemia/lymphoma rates in mice which had been fathered by plutonium-239-contaminated males. Similar results have since been obtained for the offspring of γ-irradiated fathers. Although these mice carried a history of preconception paternal irradiation (PPI), their birth weights, litter size, blood counts and general well being were normal. Nevertheless, there were parallel perturbations in their haemopoietic cell kinetics, chromosome aberration rates, and the development of their regulatory haemopoietic microenvironment. While PPI itself apparently did not directly cause leukaemia/lymphoma in the offspring, it did increase their susceptibility to a subsequent (postnatal) carcinogenic insult (in this case MNU or radiation). Thus it appeared that these mice carried some inherited latent damage that could be expressed at a later date. This article therefore examines whether inherited genomic instability, described as "a long-term change in the probability that cells will grow and divide without developing mutations in their genetic material", may have been a potential factor underlying those observations.