Effects of Continuous Gamma-Ray ExposureIn Uteroin B6C3F1 Mice on Gestation Day 18 and at 10 Weeks of Age

Abstract

Pregnant C57BL/6JJcl mice were exposed to γ rays at low dose rate (20 mGy/day, LDR) or medium dose rate (200 and 400 mGy/day, MDR) from gestation day (GD) 0-18 to total accumulated doses of 360, 3,600 and 7,200 mGy, respectively. An additional group of pregnant mice were acutely exposed to 2 Gy at high dose rate (HDR) of 0.77 Gy/min on GD 11. In experiment 1, fetuses collected via cesarean section on GD 18 were examined for external and skeletal abnormalities. While the results of LDR exposure (20 mGy/day) did not significantly differ from the nonirradiated controls in all parameters examined, MDR (200 and 400 mGy/day) and acute HDR (2 Gy) exposure caused growth retardation and significantly increased incidence of unossified bones. Increased incidence of external abnormalities was observed only in the acute HDR group. In experiment 2, the dams were allowed to give birth and the pups were clinically monitored and weighed periodically until 10 weeks of age when they were sacrificed and subjected to pathological examination. Pups exposed at MDRs of 200 and 400 mGy/dayand at acute HDR of 0.77 Gy/min had lower bodyweights from weaning (3 weeks) to 10 weeks of age except for females exposed to 400 mGy/day MDR. None of the pups exposed to an acute 2 Gy dose on GD 11 survived to 10 weeks of age. Histopathological changes were not significantly different between the nonirradiated control and the 20 mGy/day LDR groups. However, at both MDR exposures of 200 and 400 mGy/day. gonadal (testes and ovary) hypoplasia/atrophy was observed in all the 10-week-old pups. Our results show that in utero LDR exposure to 20 mGy/day for the entire gestation period did not cause any significant effect in pups when compared to the nonirradiated controls up to 10 weeks of age. However, pups exposed in utero to MDRs showed dose-related growth retardation with delayed ossifications (400 mGy/day) and gonadal hypoplasia/atrophy. These findings suggest that increased post-implantation loss in dams exposed at MDR is due to early embryonic deaths resulting in early resorption.

Effects of Continuous In Utero Low- and Medium-Dose-Rate Gamma-Ray Exposure on Fetal Germ Cells

“…We elected to use B6C3F1 mice for this study since our previously reported studies (11,34,35) also used the same strain for comparison purposes. Experiments are also underway to study the late effects, such as life span and neoplasm incidence, of chronic exposure to gamma rays in utero under similar conditions using the same strain.…”

“…Pregnant dams were randomly assigned to groups receiving wholebody gamma-ray irradiation continuously for 22 h each day from GD 0 to 18 at a LDR (20 mGy/day, total dose ¼ 360 mGy) or at MDRs (200 mGy/day, total dose ¼ 3,600 mGy or 400 mGy/day, total dose ¼ 7,200 mGy) as described elsewhere (11). The remaining 2 h were used for health monitoring of the mice and husbandry procedures, such as cleaning the rooms, cage changes with fresh bedding and providing a fresh supply of food and water.…”

“…In our recently reported study, chronic in utero irradiation for the entire gestation period (18 days) at medium dose rates (MDRs) (200 and 400 mGy/day) did not induce congenital anomalies that are often observed in the fetuses exposed to 2 Gy in utero at high dose rate (HDR) on gestation day (GD) 11. Medium-dose-rate radiation induced a mild degree of general growth retardation as evidenced by low body weight from birth (average body weight at 10 weeks of age was 89-103% of the nonirradiated controls) (11). The effects on the gonads or germ cells were striking at 10 weeks of age with the testes and ovaries weighing approximately 11-22% of the nonirradiated controls.…”

“…Animal studies have shown that the effects of acute high-dose irradiation in utero include growth retardation and congenital anomalies, including those of the central nervous system, and cognitive and behavioral abnormalities (6,7,8), as well as increased cancer incidence (9) in surviving fetuses. In several published animal studies (10), including our previously reported work (11), chronic exposures were used. Although these studies showed that chronic exposure can also induce various effects, they are usually undetectable in the lowdose-rate (LDR) range (,0.1 mGy/min or ,144 mGy/day) (12).…”

“…In this study, we have investigated the development of gonads in GD 18 fetuses that received MDR (200 and 400 mGy/day) gamma-ray irradiation in utero for the entire gestation period by examining the histomorphological changes and cell counts of germ cells in both sexes and Sertoli cell counts in males. Using these same parameters, we also analyzed the effects of the in utero chronic exposure at a LDR of 20 mGy/day wherein no gross effects were detected in our previously reported study (11).…”