Lethal and teratogenic effects in two successive generations of the HLG mouse strain after radiation exposure of zygotes — association with genomic instability?

Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

“…To date, only a limited number of studies have addressed the issue of transgenerational changes in the mammalian germ line (18)(19)(20). They have shown elevated rates of mortality and malformation in the grand-offspring of exposed males providing indirect evidence for an elevated mutation rate within the first generation.…”

Late Effects of Radiation from Conception to Adolescence: Risk in Intrauterine Irradiation, Hereditary Effects, Solid Tumours

“…Kemirgenlerde preimplantasyon aşamasındaki ışınlanma sonrası ilk maruziyet anını takip eden birkaç bölünmeden sonra artan kromozomal aberrasyonlar saptanmıştır (6). Bu genomik istikrarsızlığın gelecek nesile aktarılabilecek kalıtsal istikrarlı mutasyonlar olabileceğine dair kaygılar mevcuttur (7). İn vivo çalışmalarda organogenez döneminde ışınlanan kemirgenlerde maruz kalınan doza, gestasyonel yaşa, oksijen konsantrasyonuna, bağıl biyolojik etkinliğe göre değişen doğumsal anomaliler, büyüme geriliği ve doz yeterince yüksekse embriyonik veya neonatal ölümler gözlenmektedir (8).…”

“…Majör organogenez döneminin sonundan doğuma kadar uzanan dönemde, fetüs 3 Gy'nin altındaki dozlarda radyasyon ölümüne ve eksternal gözlenebilir malformasyonlara görece dirençli olmakla birlikte, merkezi sinir sistemi ve duyu organları, iyonize radyasyonların zararlı etkilerine karşı özellikle hassastır (6,7,8). Yaklaşık 1 Gy ışınlanma sonrasında belirgin ve kalıcı büyüme geriliği gözlenir.…”

Modeling Dose Deposition and DNA Damage Due to Low-Energy β–Emitters

“…Genomic instability is characterised by genetic changes including chromosomal rearrangements, micronuclei, transformation, gene amplifications, gene mutation, reduced plating efficiency (lethal mutations or delayed reproductive cell death) and developmental abnormalities in vivo (reviewed in Little, 1998;Morgan, 2003aMorgan, , 2003bMorgan et al, 1996;Pils et al, 1999). Although data are limited, there is some evidence that the induction of instability does not demonstrate a linear relationship to dose but is maximally induced by the lowest doses investigated, including a single alpha particle traversal (Kadhim et al, 1992(Kadhim et al, , 2001) and can lead to a substantially greater frequency of mutations than that induced by the direct action of radiation and expressed in the first one or two cell generations.…”

“…Although currently most data on radiation-induced genomic instability and radiation-induced bystander effects are from in vitro studies, the phenomena have also been demonstrated in vivo in rodents (Pampfer and Streffer, 1989;Pils at al, 1999;Watson et al, 2000Watson et al, , 2001Xue et al, 2002). Minisatellite instability has been reported in those exposed to radiation from weapons testing in Kazakhstan and in their unexposed children and grandchildren (Dubrova et al, 2002a) and in some (Dubrova et al, 1997, but not all (Livshits et al, 2001;Kiuru et al, 2003), studies after the Chernobyl accident.…”