Alteration of the p53 gene during tree shrews' hepatocarcinogenesis.
OBJECTIVE
To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1).


METHODS
Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB1; group B, only infected with HBV; group C, fed with AFB1 alone; and group D normal control. The tree shrews underwent liver biopsy every 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies.


RESULTS
The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0+/-16.6 wk vs 153.3+/-5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks 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 group D (10%) (chi2> or =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% in homology compared with those of human p53, respectively.


CONCLUSIONS
Remarkable synergistic effect on HCC exists between HBV and AFB1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.
Su
Jian-Jia
JJ
Department of Experimental Pathology, Guangxi Cancer Institute, Nanning 530021, China. jianjiasu2002@yahoo.com
Li
Yuan
Y
Ban
Ke-Chen
KC
Qin
Liu-Liang
LL
Wang
Hui-Yun
HY
Yang
Chun
C
Ou
Chao
C
Duan
Xiao-Xian
XX
Lee Yl
Young lk
Yl
Yan
Rui-Qi
RQ
D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016009:Chi-Square Distribution; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D011336:Probability; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014418:Tupaiidae
D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53