title: Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring.
abstract: It is now well accepted that parental whole body irradiation causes transgenerational genome and epigenome instability in the offspring. The majority of human exposures to radiation, such as therapeutic and diagnostic irradiation, are localized and focused. The potential of localized body-part exposures to affect the germline and thus induce deleterious changes in the progeny has not been studied. To investigate whether or not the paternal cranial irradiation can exert deleterious changes in the protected germline, we studied the accumulation of DNA damage in the shielded testes tissue. Here we report that the localized paternal cranial irradiation results in a significant accumulation of unrepaired DNA lesions in sperm cells and leads to a profound epigenetic dysregulation in the unexposed progeny conceived a week after paternal exposure.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Alberta, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Tamminga
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.forename: Mike
authors.initials: M
authors.lastname: Baker
authors.forename: Kristy
authors.initials: K
authors.lastname: Kutanzi
authors.forename: Palak
authors.initials: P
authors.lastname: Kathiria
authors.forename: Igor P
authors.initials: IP
authors.lastname: Pogribny
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sutherland
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D024201:Bystander Effect / Q000235:genetics / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects*; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000528:radiation effects*; D042822:Genomic Instability / Q000235:genetics / Q000528:radiation effects; D005854:Germ Cells / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009154:Mutation / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors; D013090:Spermatocytes / Q000473:pathology / Q000528:radiation effects; D013737:Testis / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D013950:Thymus Gland / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects