Evaluation of the cytogenetic damage and progenitor cell survival in foetal liver of mice exposed to gamma radiation during the early foetal period

Purpose: To investigate the haemopoietic response to low dose gamma irradiation at the early foetal period when the liver is the major haemopoietic organ. Materials and methods: Pregnant Swiss albino mice were exposed to 0.1-1.5 Gy of gamma radiation on the 14th day of gestation. Twenty-four hours (15 day post conception (p.c.)) and 72 h (17 day p.c.) after exposure, the foetuses were dissected out, weighed, and liver weight and mean cellularity were determined. Cytogenetic damage in liver cells was assessed by chromosome aberration analysis and micronucleus (MN) count. The haemopoietic progenitor cell survival at 24 h and 72 h after exposure was measured by exogenous spleen colony assay on day 8 (CFU-S₈) and day 12 (CFU-S₁₂) after intravenous injection of the foetal liver cells into adult bone marrow-ablated recipient mice. Results: The foetal body weight at 24 h after exposure showed a significant reduction at doses of 0.5 Gy and above, while the 72 h body weight was significantly lower than control from 0.3 Gy onwards. Liver weight showed a similar reduction for doses from 0.25 to 1.5 Gy at both the post-irradiation observation times. However, when liver weight/body weight ratios were compared, there was no significant difference between the irradiated and control values. Total liver cellularity at 24 h and 72 h after exposure showed a dose-dependent decrease, with significant depletion from control at 0.25 Gy and above. When donor cells were taken at 24 h after exposure (15 day p.c.) the CFU-S₈ showed a significant decrease only at 1.0 and 1.5 Gy, while the CFU-S₁₂ suffered such a depletion at 0.25-1.5 Gy. For donor cells recovered at 72 h after exposure, both CFU-₈ and CFU-S₁₂ decreased linear-quadratically with radiation dose and were significantly lower than control at 0.25 Gy. A significant increase in the percent aberrant metaphases and micronucleus counts was seen at 0.1 Gy and 0.15 Gy, respectively, and increased linear-quadratically with radiation dose. Conclusions: The results demonstrate that the liver, which is the major haemopoietic organ at the early foetal period, is highly sensitive to radiation damage from maternal irradiation. At low doses, the lethal effect on the haemopoietic stem cells appears to develop more slowly than at higher doses.