The influence of croton oil and of polyethylene glycol-400 on carcinogenesis in the forestomach of the mouse.

nism†• of carcinogenesis (3, 4,) is largely based on experimental studies on skin (6, 12, 14), though some evidence is already available for its applica bility to the thyroid gland (8, 11) and the liver (10). The extension of the problem to gastric carcinogenesis is of particular interest (a) because of the clinical importance of cancer of the stomach and the total lack of information about its etiology in man and (b) because of the wealth of informa tion available about the normal functioning of the gastric mucosa, which might provide a more physiological approach to the problem than was possible in the case of the skin. The failure to induce tumors of the glandular mucosa of the stomach in mice by feeding carcino gens, even after many attempts to improve the technic (5), led to a shift in emphasis from the glandular mucosa to the squamous epithelium of the forestomach. Unfortunately, the experimental procedure designed for the two-stage mechanism of the glandular mucosa was not ideally suited for that of the squamous epithelium. The use of high concentrations of carcinogen given on an empty stomach, intended to encourage the develop ment of the initiating stage of carcinogenesis in the glandular mucosa, was more than adequate to complete the entire carcinogenic process in the squamous epithelium of the forestomach. For the study of the two-stage mechanism in the latter, these doses were obviously too high for a clear-cut demonstration of promoting effects by agents ad ministered subsequently. Nevertheless, the results obtained were suf ficiently interesting and unexpected to justify their publication in their own right, apart from any light they might throw on the two-stage mechanism. The methods were as described in the preceding communi cation (5), except that the one, two, or three weekly feedings * This work was supported in part by grants from the Da mon Runyon Fund (1951†" 58). of carcinogen (referred to as ‘‘primarytreatment†•) were fol.. lowed, after a 8-week interval, by the â€oesecondary treat ment,†• which consisted of 30 weekly feedings of 0.8 ml. of 1 or 8 per cent croton oil in polyethylene glycol-400, or of the solvent alone, with additional control groups as described in the rele vant sections. As before (5), the animals were male mice, about 8 months old at the start of the experiments, of C3H or Swiss strain, bred in this laboratory by brother-to-sister …