Interactive Effects Between Viruses and Chemical Carcinogens

Abstract

The concept of multistage carcinogenesis was largely formulated by investigators observing the interactive effects of viruses and chemicals. Rous and his coworkers (Rous and Kidd 1938; Rous and Friedewald 1944) found that virally induced skin papillomas that had regressed could be made to reappear by chemical irritants and concluded that the induced growth of these latent or dormant tumor cells occurred by a different mechanism (tumor promotion) than tumor induction (tumor initiation). Berenblum and Shubik (1947) more precisely divided carcinogenesis into initiation and promotion stages, and today the development of cancer is considered to be a multistep process involving several genetic and epigenetic steps (Boutwell 1974; Cairns 1975). Viruses are able to act at various stages of carcinogenesis, and interactive effects between environmental chemical carcinogens and viruses may be of substantial importance in human carcinogenesis (Fig. 1). Viral infections are widespread in humans, and viruses are factors in several types of human cancer, e.g., Burkitt’s lymphoma, nasopharyngeal cancer, liver cancer, T-cell leukemia, skin cancer, and cervical cancer (for review, see Phillips 1983). The purpose of our review is to summarize the current status of laboratory and epidemiological studies designed to investigate interactive effects of viruses and chemicals in carcinogenesis (Table 1).