CLAYSON, Lawson, Santana and Bonser (1965) suggested that in the mouse the oral administration of chemical bladder carcinogens induced hyperplasia of the bladder epithelium in the first days or weeks of the experiment. Subsequently, Clayson and Pringle (1966) showed that the number of mitoses in the normal adult mouse bladder epithelium is very low and suggested that it is necessary to increase the mitotic rate in order to induce tumours. They showed that the implantation of a paraffin wax or cholesterol pellet, or a small glass bead, into the lumen of the bladder increased the mitotic rate. Subsequently, Clayson, Pringle and Bonser (1967) found that a single oral administration of 4-ethylsulphonylnaphthalene-1sulphonamide, a murine bladder carcinogen, greatly increased the number of mitoses in the bladder epithelium, while Wood (personal communication) observed a smaller increase in mice given 2-acetamidofluorene in the diet. Thus, the correlation of early hyperplasia and subsequent malignancy can be explained on the grounds of an initial increase in the number of mitoses in the bladder epithelium. In the course of the experiments of Clayson et al. (1965) a number of chemical
