Let us forget "tumour promotion" and start thinking about mechanisms of non-genotoxic carcinogenicity

Both genotoxic and non-genotoxic mechanisms may contribute to carcinogenesis. Each may be effective by itself, or the two may act in any combination to boost the risk of neoplasia. Non-genotoxic carcinogens may act in a wide variety of ways and not simply as second stage carcinogens (i.e. promoters) on previously initiated cells. There is no justification for assuming that cancers have to be "initiated" by genotoxic carcinogens. Prior exposure to a genotoxin is obviously not necessary for hormonal carcinogenesis in which evidence of DNA damage occurs as a late, and not an early, event. Perhaps hormone-induced hyperplasia renders cells more sensitive to environmental or endogenous genotoxins? New data indicating that overnutrition predisposes to increased mortality from malignant neoplasms of a wide variety of kinds in rats is briefly presented. It is suggested that the use of the terms "initiator" and "promoter" should now be phased out in favour of "genotoxic carcinogens" and "non-genotoxic carcinogens", respectively.