Low dose fetal irradiation, chromosomal instability and carcinogenesis in mouse

A study was carried out to see if acute low dose fetal irradiation of mouse could induce long lasting chromosomal anomalies and adult cancers. The abdomen of pregnant Swiss mice was exposed to 0.1–1 Gy of ⁶⁰Co gamma radiation on day 14 of gestation. The animals were killed 24 h later or allowed to deliver their young. Hemopoietic cell death and chromosomal aberrations were studied in the fetal liver. Chromosomal instability was traced in the 1 Gy exposed group from the fetal liver cells through their CFU-S to postnatal bone marrow. The F1 mice were observed for chromosomal aberrations in the bone marrow and for solid tumor incidence. Irradiation produced a significant dose-dependent increase in the hemopoietic cell death and aberrant metaphases in the fetal liver. The main types of aberrations were chromatid breaks and fragments. The aberrations persisted in the spleen colonies developed from these cells. Their frequency decreased in the postnatal bone marrow, however, showed a significant increase at 12 months of age. Some exposed animals had abnormally high leukocyte counts and after 1 Gy their bone marrow had eight times more polyploid cells than the control. Prenatal exposure also significantly increased the incidence of solid tumors, the ovaries showing the highest risk. It is concluded that a single exposure below 1 Gy of gamma radiation at the early fetal stage of these mice can induce persistent chromosomal instability in the hemopoietic cells, and significantly increase the incidence of solid tumors in adults.