Dose and dose rate effect in mutagenesis, teratogenesis and carcinogenesis

摘要

In utero exposure to X-rays, ~(60)Co 7-rays, ~(252)Cf neutron, and 3~H water resulted in the linear increase of in vivo somatic mutation in PTHTFj 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 7-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 7-ray-induced mortality, malformation and leukemia. The double-strand break repair plays anessential 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.