title: Interactive effects of chemical carcinogens and hepatitis B virus in the pathogenesis of hepatocellular carcinoma.
abstract: Liver cancer is one of the most prevalent forms of cancer in the world. Hepatitis B virus (HBV) is considered to be a major aetiological factor. Evidence from epidemiological studies has also indicated that environmental contaminants such as mycotoxins may, either in combination with HBV or independently, be important aetiological factors in the pathogenesis of primary hepatocellular carcinoma (PHC). Laboratory data also suggest an interplay between viral and chemical factors in the multifactorial aetiology of PHC. Aflatoxin B1, the chemical carcinogen most frequently implicated in the aetiology of hepatocellular carcinoma is a procarcinogen that must be activated by mixed-function oxidases to an electrophilic metabolite before it can exert its carcinogenic effects. Interindividual differences (greater than 10-fold) in the metabolic activation of aflatoxin B1 are observed. These differences may play a part in an individual's oncogenic susceptibility to aflatoxin B1. Chemical carcinogens and integrated HBV may activate cellular oncogenes, eg N-ras, and inactivate tumour suppressor genes. Recently developed methods that allow monitoring of aflatoxin B1 and HBV exposures and also genetic damage caused by these agents in individuals should help in biochemical and molecular epidemiological studies concerning the aetiology of hepatocellular carcinoma. We identify areas of uncertainties and of future experimentation and propose a hypothesis of liver carcinogenesis.
mesh_terms: D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D016604:Aflatoxin B1