Abstract
We studied a mechanism of the p53 gene that protects against radiation-induced teratogenesis using p53(-/-) mice, p53(+/-) mice and p53(+/+) mice. In p53(+/+) mice, p53-dependent and independent DNA repair mechanisms combined to restore damaged DNA, and unrestorably damaged cells were effectively removed by p53-dependent apoptosis after low dose rate irradiation. In this model, the teratogenic rate is controlled. In contrast, in p53(-/-) mice, p53-independent DNA repair mechanisms worked, but p53-dependent DNA repair mechanisms and apoptosis did not work. Therefore, the teratogenic rate does not decrease to a controlled level, even at low dose rate irradiation in p53(-/-) mice. Irradiation-induced DNA damage is thought to provoke similar mechanisms in the processes of carcinogenesis and teratogenesis.
In this study we investigated whether the p53 gene functions to remove damage not only via DNA repair mechanisms, but also via apoptosis in the carcinogenesis process. In p53(+/+) mice, if repair of DNA damage and removal of damaged cells by apoptosis is complete after repetitive low dose irradiation, then cancer may not arise. Under the same experimental conditions, if the cancer appears in p53(-/-) mice, perhaps there is a threshold dose of radiation that induces the carcinogenesis process.
Method: Seven-week-old mice were used. The backs of the mice were irradiated with beta-rays three times a week throughout the life of the mice.
Source: 90Sr-90Y disk source, 1.85GBq, 15Gy/min.
