Forestomach carcinogens: possible mechanisms of action

A brief review indicates that a considerable number of compounds induce forestomach tumours in different species. Naturally occurring forestomach tumours are rare (an incidence of less than 1%) in rats and mice, but they do occur in hamsters with incidences up to 12%. Most forestomach carcinogens are known to be genotoxic, although a few non-genotoxic substances are also able to induce this type of tumour. The promoting and inhibiting action of substances in a two-stage forestomach tumour model is described. Morphologically the development of tumours is characterized by early lesions such as epithelial damage, hyperplasia and hyperkeratosis, which at a later stage progress to strong diffuse hyperplasia, dysplasia, papilloma and squamous-cell carcinoma. Possible mechanisms of action of non-genotoxic forestomach carcinogens are described, and the relevance to man is discussed. Since humans have no squamous epithelium in the stomach, the potential risk from non-genotoxic forestomach carcinogens involves exposure of the mouth, pharynx and oesophagus at dose levels that exert irritating action. It seems very unlikely that exposure to concentrations far below those having irritating potential is hazardous to man.