Influence of Interrupted Carcinogenic Treatment on Tumor Formation. ∗

Abstract

Summary

The influence of interrupted carcinogenic treatment on tumor formation was tested. Rest periods of from one to 3 months were interspersed between 2 periods during which the carcinogens were applied to mice at minimal carcinogenic levels. The investigation was divided into two parts on the basis of the carcinogens employed. In one, ultraviolet irradiation was used for both the first and second periods. In the other, methylcholanthrene was employed to initiate the process and croton oil, a non-carcinogenic substance, was used to evoke the neoplasms. The results with both technics were essentially the same.

A lag in tumor appearance was observed during the rest periods, and the second period of treatment quickly brought forth tumors in the precarcinogenic areas. Essentially no difference in the rate of tumor formation or in the final tumor incidence was observed when the rest period was of one month duration. When the rest period was increased to 3 months, the final tumor incidence was reduced by 34% in the mice irradiated and by 42% in those in the methylcholanthrene-croton oil series. The results indicate that the initial application of the carcinogen produced alterations in the tissues which were maintained for at least one month, thereafter the changes reverted toward normal. It is suggested that the genesis of the neoplastic cell was completed during the initial treatment, and such cells remained dormant or divided at a decreased rate until further stimulated. The non-specific irritant, croton oil, exerts its effect during the critical period of carcinogenesis.