Dependence of Malformation upon Gestational Age and Exposed Dose of Gamma Radiation

Abstract

In order to evaluate the importance of gestational age and the dose-incidence relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5 to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also at day 11.5 after conception, which was the most sensitive stage for the induction of major congenital malformations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. The only demonstrable effect of irradiation during the pre-implantation period was an increase in prenatal mortality. Resorptions were maximal on exposure at day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. A small head, growth retardation, a cleft palate, dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the extremities and tail after exposure were prominent during the organogenesis period, especially on day 11.5 of gestation. As for the dose-incidence relationship, the incidence of a small head, growth-retarded fetuses, a cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose as the radiation dose increased. The result indicated that the late period of organogenesis in the development of the brain, skull and extremities of a mouse was a particularly sensitive phase. The threshold doses of radiation that induced a cleft palate and dilatation of the cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively.

A detailed characterization of congenital defects and mortality following moderate X‐ray doses during neurulation

“…Our findings do support the study by S.H. Kim et al, who observed an elevated number of resorptions in the E7.5 group after exposure to gamma rays (2 Gy) in ICR mice (Kim et al, ). Dose‐dependent fetal weight loss at E18 was reported by Di Majo as well, following exposure to X‐irradiation (0.0–2.0 Gy) at the neurulation stage (E7.5), thus supporting our data (Di Majo et al, ).…”

“…Kim et al reported that high dose (2.0 Gy, 10 Gy/min) gamma irradiation of pregnant ICR mice during discrete stages of development induced the highest incidence of gastroschisis after irradiation at E7.5 (2.22%), which is in accordance with our results obtained with X‐rays. Interestingly, in their study the most radiosensitive stage for developing cleft palate was identified as E11.5 (36.59%), whereas we observed the highest incidence at E7.5 (Kim et al, ). Continuing, in swiss albino mice irradiated with 0.5 Gy Gamma rays, open eye defects were also found to be significantly more prevalent after irradiation at E17, suggesting that the induction of both cleft palate and open eye defects is not limited to irradiation during neurulation (Hossain, Devi, & Bisht, ).…”

Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems

“…Regulation of the embryonic cell cycle as influenced by induced damage is one aspect of translating the rates of CA, as observed in our study, with the developmental profiles in vivo, as for instance observed by Kim et al [4] and indicated before Heyer et al [3]. ES cells do not show a G1-S checkpoint, yet are sensitive to apoptosis (see in [46]).…”

“…These authors showed this process to be ATM-and p53-dependent, demonstrating cell cycle checkpoints to be active. In line with this sensitivity for DNA damage-induced apoptosis, Kim et al [4] found that when determining prenatal death from 2 Gy gamma irradiation at prenatal days 2.5, 5.5, 7.5, 11.5 and 15.5, greatest sensitivity was observed at the morula stage, followed by gastrulation at day 7.5 (resp. 66% and 45% death).…”

Protection of the Gametes Embryo/Fetus From Prenatal Radiation Exposure

“…Many other investigators have confirmed these findings, including Kim et al (2001), indicating no increase in malformations or growth retardation in mice following 2 Gy (gamma rays) at a preimplantation stage. Mole (1993) concluded that the preimplantation period is not a stage where an increase in viable malformations will result from irradiation.…”