Abstract
The p53 gene encodes a tumor suppressor protein, and it is generally believed that there is a dosage effect for the p53 gene. To examine this gene-dosage effect, we looked at the incidence of cancer and latent period of carcinogenesis in irradiated p53 wild type (+/+), heterozygous (+/-), and knockout mouse (-/-). Using beta rays, we repetitively irradiated the skin of p53 (+/+), (+/-), and (-/-) mice to examine carcinogenesis. Since the lifespan of the p53 (-/-) mouse was short, we were not able to observe any carcinogenesis, but for the (+/+) and (+/-) mice, results showed that (+/+) > (+/-) on the latent period of carcinogenesis, and (+/+) < (+/-) for cancer incidence. When we examined mutation and loss of heterozygosity (LOH) of the p53 gene on obtained tumors, approximately 61% of the (+/-) mouse tumors showed LOH, but there was no mutation. In the (+/+) mouse tumors, mutations occurred in about 78% and LOH was about 33%. These results indicate that there is no dosage effect for the p53 gene protein. However, it is possible that carcinogenesis occurs through different processes based on the status of the p53 gene. Variations in the carcinogenesis process may affect not only the presence and quantity of the gene products for carcinogenesis, but also the status of the genes themselves.
