Dose and dose rate effect in mutagenesis, teratogenesis and carcinogenesis

Abstract

In utero exposure to X-rays, 60Co γ-rays, 252Cf neutron, and 3H water resulted in the linear increase of in vivo somatic mutation in PTHTF 1 mice, while tumors were induced in the offspring after the postnatal treatment with tumor promoter. Apparent dose rate effects were observed in X-ray-induced mutation, malformation and tumor. In the young adult mice exposed to 0.4–6.8 Gy of γ-rays at the dose rates from 0.04 to 1189 mGy/min at the same age, a large and significant reduction of leukemia was observed by the low dose rate exposure, while dose rate effects were not detected in solid tumors at high doses. However, a significant reduction in the incidences of solid tumors was observed at low dose (0.4 Gy) and low dose rate (0.04 mGy/min) exposure. Double-strand break repair deficient SCID (severe combined immunodeficient) mice were extremely sensitive to radiation, and no dose rate effects were observed in γ-ray-induced mortality, malformation and leukemia. The double-strand break repair plays an essential role in homeostasis of the organism. In the normal human tissues maintained in the improved SCID mice, daily UV-light B exposure-induced mutation, keratosis and skin cancer. However, cancer has not been induced in the human thyroid gland below 60 Gy of X-rays, although p53 and c-kit mutations were detected at lower doses.