ABSTRACT

This chapter explains the properties of chemicals that have induced colon cancer in animal models, especially with one dose, or with a few pulse doses, and briefly alludes to the modification of their effect as a function of species, strain, sex, intestinal flora, and nutritional status. It describes the metabolism and mode of action of these colon carcinogens. H. Druckrey discovered that 1,2-dimethylhydrazine (DMH) was best injected s.c. or given orally at fairly large doses in order to induce colon cancer. On a molar basis, azoxymethane is a more effective carcinogen than DMH, in great part because it is closer to the proximate and ultimate carcinogens in this sequence of metabolic reactions. The proximate carcinogen derived from DMH is methylazoxymethanol, which occurs as the natural product cycasin in the nut of certain species of the cycad tree, in the form of the β-glucoside of methylazoxymethanol.