Alteration of the p53 gene during tree shrews' hepatocarcinogenesis

摘要： <正> OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of treeshrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1).METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed withAFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control.The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected byimmunohistochemistry and molecular biotechnologies.RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than ingroups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wkvs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%,60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in groupD (10%) (X~2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C.The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13.Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% inhomology, compared with those of human p53, respectively.CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 maysynergistically induce p53 gene mutation. ... （共5頁）