JuLL (1951) suggested that the surgical introduction of a pellet containing a test chemical into the lumen of the mouse bladder might be useful for routine testing for carcinogenic activity. The method, it was thought, would possess the following advantages: (i) the chemical would be slowly eluted from the pellet and would therefore remain in contact with the bladder epithelium for a prolonged period; (ii) the metabolic processes of the liver, etc., would be by-passed, and (iii) the bladder would function under approximately normal conditions.Bladder implantation has been used successfully in Leeds Jull, 1958, 1963), in London (Allen, Boyland, Dukes, Horning and Watson, 1957) and in Madison (Bryan, Brown and Price, 1964a, b).The advantages predicted for the technique have not been completely fulfilled. Chemicals have been shown to diffuse from pellets at different rates (Bryan, Brown, Morris and Price, 1964), although there was no correlation between rate of diffusion and carcinogenicity of a series of chemicals. The bladder epithelium has been shown to be permeable to certain chemicals (Bryan, Morris and Brown, 1965;Pringle, 1966), and so it cannot be assumed that metabolism by the liver with consequent excretion of metabolites is necessarily excluded by the use of bladder implantation. Furthermore, the presence of a foreign body, the pellet, in the bladder lumen affects the response of the epithelium to a carcinogen (Bryan and Springberg, 1966) probably because it induces mitosis in the bladder epithelium (Clayson and Pringle, 1966). The pellet by itself usually leads to a background incidence of tumours (Bonser et al., 1958).The purpose of this paper is to present new information on the testing of chemicals by bladder implantation and to reassess the utility of the method.The chemicals investigated consist of aromatic amines and their derivatives, hydrocarbons and dyestuffs.
MATERIALS AND METHODSAnimals.-C57 x IF F1 hybrid mice were bred in the laboratory and maintained on Oxo Diet 41B and water, ad libitum. They were 10-12 weeks of age at the start of the experiment.Bladder implantation was carried out by the method of Jull (1951) as modified by Allen et al. (1957). Except where otherwise stated, the experiments were terminated at 40 weeks and the bladders prepared for histology in the usual way. The histological grading of the tumours was assessed by the criteria of Bonser and Jull (1956).