Hepatocellular Carcinoma and Possible Chemical and Biological Causes: A Review

The development of hepatocellular carcinoma (HCC) is a multistep process. In HCC, progressive and morphologically distinct preneoplastic lesions/alterations associated with chronic liver injury, inflammation, hepato-cellular degeneration/regeneration, necrosis, and small-cell dysplasia can be observed. The incidence of HCC exhibits regional and ethnic differences. Several cytotoxic and DNA-damaging chemicals are suggested to be the underlying causes of HCC-for example, acrylamide, perfluorooctanoic acid (PFOA), polychlorinated biphenyls (PCBs), ben-zo(a) pyrene (BaP), perfluorinated chemicals (PFCs), vinyl chloride monomer (VCM), and dietary contaminants (aflatoxins, ochratoxins). Also suggested are substances of abuse (alcohol) and biological agents, such as hepatitis B and C and human immuno-deficiency virus 1 (HIV-1). These can act through genetic and/or epigenetic mechanisms. This review will shortly address the genetic and epigenetic mechanisms of HCC and focus on cytotoxic and DNA-damaging chemicals and biological agents, exposure to which are suggested to lead to HCC initiation, promotion, and/or progression.