gamma-ray induced hepatocarcinogenesis in p53-deficient mice

Background: Mutations in the p53 gene are frequent genetic alterations in h uman hepatocellular carcinoma (HCC), but, little is known of the molecular genetic changes that occur during murine hepatocarcinogenesis. Materials an d Methods: To characterize the properties of constitutive p53 deficiency th at contribute to fiver tumor development, a total of 168 Fl mice of two dif ferent strains (C3H, which are susceptible to hepatocarcinogenesis and MSM [Mus. M. molossinus] with a single null p53 allele) were exposed to a singl e 3-Gy dose of whole-body gamma-irradiation at 4 weeks of age and observed for a period of 360 days. The genotype of the mice and the p53 spectrum of the tumors were investigated by polymerase chain reaction (PCR) analysis. R esults: Thirty-five gamma-ray-induced HCCs were obtained as a result of thi s experiment. 11 (40%) of the mice with liver tumor were wild-type for p53. All liver tumors examined retained the wild-type p53 allele, indicating th at p53 itself may nor be a target for radiation-induced alteration. Only tw o p53-deficient mice in the liver tumor group developed thymic lymphomas. T he p53-deficient mice showed no significant differences in the number, size , or growth rate of HCC or in the apparent development of HCC. Conclusions: These results indicate that p53 deficiency does not enhance the rate of de velopment ol degree of malignancy of radiation-induced HCC in mice but may instead favor the development of multiple primary cancers.