Animal Tests for Carcinogenesis: Relevance for Man

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Abstract
The theory that all carcinogens are mutagens has been disproved. Numerous nongenotoxic mechanisms are implicated in carcinogenesis. It is inconceivable that a single simple short-term test can be developed to predict nongenotoxic carcinogenicity. Pro longed disturbance of physiological and/or hormonal status may predispose to increased cancer risk. Overnutrition leads to a variety of physiological and hormonal disturbances in rats. It also predisposes to the early onset of ageing-related diseases and the development of a wide variety of benign and malignant neoplasms. It is suggested that overnutrition is associated with increased endogenous generation of electrophiles, which, on the one hand, age cells and tissues, and on the other, overwhelm the normally efficient DNA repair mechanisms. It is further suggested that hormones predispose to cancer by stimulating cellular proliferation and metabolic rate in target tissues. Thus, nongenotoxic mechanisms of carcinogenesis do involve DNA damage, but do so as a late stage rather than as a first event. The two-stage theory of carcinogenesis is misleading in this respect. Careful studies of the relationships between ageing and cancer risks are long overdue.