The Mechanism of Carcinogenesis A Study of the Significance of Cocarcinogenic Action and Related Phenomena

In a previous communication (5), the author has shown that when the effective carcinogenic potency of 3,4-benzpyrene for the mouse's skin was reduced by application of the hydrocarbon in a dilution ot~ o.o 5 per cent, the low tumor yield (o to 6 per cent at the 2oth week) was increased to 80 per cent by application of croton resin concurrently with the benzpyrene. 1 This augmentation of carcinogenesis, or "cocarcinogenie action," could not be explained as a summated effect of two weak carcinogens, since croton resin gave no decisive evidence of carcinogenicity when applied alone to the skin. Nor could the effect be attributed to a nonspecific irritative action on the part of croton resin, since other skin irritants, such as xylene or turpentine, failed to augment carcinogenesis under similar conditions. It was suggested, therefore, that the cocarcinogenic effect of croton resin constituted a specific reaction distinct from the carcinogenic process itself. Yet the mechanism of cocarcinogenic action remained unexplained. The present communication is concerned with an extension of this work, certain problems having been chosen for special study as likely to throw light on the nature of cocarcinogenic action and on its relation to the normal process of carcinogenesis. The problems chosen for investigation were the following: i. The effect of croton resin on carcinogenesis of the skin by concentrated solutions of weak carcinogens; 2. the effect of croton resin on carcinogenesis associated with injections of benzpyrene; 3. the effect of croton resin applied to the skin before or after a limited period of benzpyrene application; and 4the effect of croton resin on the malignant transformation of skin tumors induced by benzpyrene. The methods employed in these experiments were essentially the same as those previously used by the author, and need not, therefore, be described again in