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Synergistic interactions between chemical carcinogens, tumor promoters, and viruses and their relevance to human liver cancer.

This paper reviews evidence from experimental animal model systems and tissue culture systems in which viruses or virus-encoded genes interact synergistically with specific environmental chemicals to cause malignant cell transformations. These synergistic interactions include both DNA and RNA viruses and chemicals that have genotoxic (DNA-damaging) activity or are nongenotoxic tumor promoters. They also include both fibroblast and epithelial and both rodent and human cell systems. In many cases, the precise mechanisms are not known but examples are described in which specific virus-encoded genes interact with the products of cellular oncogenes, a tumor suppressor gene, or cellular signal transduction pathways. Recent evidence that DNA damage by chemical agents and irradiation can induce trans-acting factors that enhance viral DNA synthesis is also described. Finally, the relevance of these chemical-viral synergistic interactions to the causation of liver cancer and other forms of cancer in humans is discussed. Such synergistic interactions could be directly relevant to new strategies for cancer prevention.