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

Journal of Radiation Research, Sep 2001

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.

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

SUNG HO KIM 2 JONG HWAN LEE 2 HEON OH 2 SE RA KIM 2 CHA-SOO LEE 1 SUNG KEE JO 0 TAE-HWAN KIM 3 YUN-SIL LEE 3 0 Food Irradiation Team , KAERI, Taejeon, Korea 1 College of Veterinary Medicine, Kyungpook National University , Taegu, Korea 2 College of Veterinary Medicine, Chonnam National University , Kwangju, Korea 3 Laboratory of Radiation Effect, Korea Cancer Center Hospital , Seoul 139 -706, Korea (Received, October 4, 2000) (1st. Revision received, January 9, 2001) ( 2nd . Revision received, April 2, 2001) (3rd. Revision received, April 30, 2001) (Accepted, May 15, 2001) Dose relationship/Gestational age/Radiation/Mice/Abnormalities 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. INTRODUCTION The irradiation of mammalian embryos can produce a spectrum of morphological changes, ranging from a temporary stunting of growth to severe organ defects and death1). During the period of major organogenesis, mammalian embryos are extreamly susceptible to radiation-induced gross anatomic abnormalities; this period spans 7 to 12 days p.c. in mice, corresponding to about 14 to 50 days in humans2). The induced abnormalities depend on the organs undergoing proliferation and differentiation at the time of irradiation, the stage of proliferation and differentiation and radiation dose35). The effect of irradiation during the early period of murine development, such as the onecell to blastocyst stage, has been extensively studied in vitro by Streffer and co-workers6,7) and in vivo by Russell, Rugh and others811). In the past, the induction of malformations resulting from exposure to radiation during major organogenesis and early fetal periods had received considerable attention in radiation embryology8,1216), and still continues to a focus of study1720). However, Mole argued in a review that the concept of critical periods based on a marked response at high doses of radiation may not be applicable to lower doses21). Furthermore, although numerous studies on radiation teratology have been published22), there is relatively little information available on the relationship between radiation dose and the incidence of specific abnormalities. This led us to carry out a systematic study on the highly sensitive prenatal periods and dose-incidence related to radiation. MATERIAL AND METHODS Animals ICR mice maintained under controlled temperature, light conditions, on standard mouse food and water ad libitum were used in the experiment. Virgin females and males, 1012 weeks of age, were randomly mated overnight. Females with a vaginal plug were separated in the morning and marked as 0 day pregnant. All of the mice were killed on day 18 p.c. by cervical dislocation. Irradiation The pregnant mice were exposed to 2.0 Gy gamma-radiation at a dose-rate of 10 Gy/min on any one gestation day from 2.5 to 15.5 days p.c., and the dose-incidence relationships with 0.5, 1.0, 2.0 and 4.0 Gy of gamma-radiation were investigated on day 11.5 after conception. Prenatal mortality Uterine horns were opened and the total number of implantations including resorption, embryonic death and fetal death were examined. These were: (A) resorptions including (a) implantation failure in which the implantation site was shown by a rudimentary fleshy mass, but not a full placentum, and (b) a placentum without attached embryonic rudiments. (B) Embryonic death: a partly formed em (...truncated)


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Sung Ho Kim, Jong Hwan Lee, Heon Oh, Se Ra Kim, Cha-Soo Lee, Sung Kee Jo, Tae-Hwan Kim, Yun-Sil Lee. Dependence of Malformation upon Gestational Age and Exposed Dose of Gamma Radiation, Journal of Radiation Research, 2001, pp. 255-264, 42/3, DOI: 10.1269/jrr.42.255