Human hepatitis B virus and hepatocellular carcinoma II. Experimental induction of hepatocellular carcinoma in tree shrews exposed to hepatitis B virus and aflatoxin B1

Abstract

On the basis of the successful establishment of an animal model in tree shrews experimentally infected with human hepatitis B virus (HBV), a study on the hepatocarcinogenic effects of HBV and/or aflatoxin B1 (AFB1) was conducted. The results showed that the incidence of hepatocellular carcinoma (HCC) was significantly higher in the animals both infected with HBV and exposed to AFB1 (52.94%) than in those solely infected with HBV (11.11%) or exposed to AFB1 (12.50%). No HCC of precancerous lesions were found in the controls that were neither HBV-infected nor AFB-1 exposed. Precancerous lesions, including liver cell dysplasia and enzyme-altered hyperplastic hepatocyte foci, were observed before the occurrence of HCC, and the frequency of their appearance correlated well with the incidence of HCC. HBV DNA and the protein it encodes were detected in the cancer cells and/or the surrounding hepatocytes. Integration of HBV DNA into the host liver genome was found during hepatocarcinogenesis among the animals infected by HBV. These results suggest that exposure to HBV and AFB1 may play a synergistic role in the development of HCC, and support the viewpoint of an aetiological relationship between HBV and HCC.

Genome of the Chinese tree shrew

“…Except for chimpanzees, there are many reports that tree shrew and its hepatocytes could be infected with human HBV 4 and HCV 3 . Hence, the property of genes involved in immunity response of viral infection demonstrated by tree shrews further contributes to their preferred choice as an attractive model for studying viral hepatitis and hepatocellular carcinoma 35 . Here, the available tree shrew genome data offer a distinct advantage to scan these immune genes involved in viral hepatitis.…”

Activation of the insulin-like growth factor II transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma

“…In accordance with this, more than 50% of all HCCs from geographic regions with a high dietary AFB1 exposure contain p53 mutations in codon 249 (Hsu et al, 1991;Bressac et al, 1991). Studies on the hepatocarcinogenic eects of HBV and/ or AFB1 on tree shrews (Tupaia glis) showed that the incidence of HCC was signi®cantly higher in animals both infected with HBV and exposed to AFB1 than in animals only infected with HBV or exposed to AFB1, suggesting that exposure to HBV and AFB1 may play a synergistic role in the development of HCC, supporting the idea of an etiological relationship between HBV and AFB1 (Yan et al, 1996;. A number of studies have demonstrated the modulation or abrogation of the wild-type p53 function by mutant p53s.…”

Animal models as a tool in hepatocellular carcinoma research: A Review

“…34,194 Some human hepatitis virus-infected chimpanzee (Pan troglodytes), tree shrews (Tupaia belangeri chinensis), and rhesus macaques (Macacca mulatta) also developed HCC mainly when combined with chemical carcinogens. 34,195,196 Concerning rhesus macaques, neoplasia in juvenile is extremely uncommon. A recent case report of naturally occurring neoplasia and metastatic liver was identified in a 3.75-year-old primiparous female rhesus macaque.…”