A review of molecular mechanisms in the development of hepatocellular carcinoma by afatoxin and hepatitis B and C viruses

摘要

Afatoxins are food-borne secondary fungal metabolites that are hepatotoxic, hepatocarcinogenic, and mutagenic. Urinary and serum biomarkers are more effcient in refecting dietary exposure to afatoxin B1 (AFB1) than other methods such as food sampling and dietary questionnaires. Chronic infection of the hepatitis B virus (HBV) and dietary exposure to AFB1 are the major risk factors in a multifactorial etiology of hepatocellular carcinogenesis, raising the possibility of a synergistic interaction between 2 agents. These effects are due to the formation of DNA and protein adducts and lipid peroxidation. Most patients with hepatocellular carcinoma and HBV infection had prevalent GC → TA transversion mutation at the third position of codon 249 of the p53 gene. The HBx protein of HBV also promotes cell cycle progression, increases the expression of telomerase reverse transcriptase, inactivates negative growth regulators, and binds to and inhibits the expression of p53 (antiapoptotic activity) and other tumor suppressor genes and senescence-related factors. Some reports also evidence the role of hepatitis C virus in the pathogenesis of HCC. Inhibitors of AFB1 adducts are found to be potent chemoprotective agents against AFB1-induced HCC. This review focuses on the interaction of afatoxin, HBV, and hepatitis C virus in the development of HCC.