Diaplacental carcinogenesis: tumor localization and tumor incidence in NMRI mice after diaplacental initiation with DMBA and urethane and postnatal promotion and the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment.

Abstract

Diaplacental initiation with the carcinogens DMBA or urethane followed by repeated topical treatment of mice of the F1 generation with the tumor promoter TPA leads to the formation of benign and malignant tumors on the skin of the back as well as in other tissues and organs. The tumor yield in this modified 2-stage Berenblum/Mottram experiment considerably exceeds the number of spontaneously formed tumors and of tumors produced by initiation alone. Further differences can be demonstrated in the malignancy rate, the formation of multiple tumors in various organs, additional non-neoplastic alterations and in a reduction of the lifetime of the animals. The effect of the tumor promoter TPA is not restricted to carcinogenesis in the back skin. Obviously, TPA is able to activate inititated tumor cells in internal organs to form tumors. This, in turn, implies the absorption of the substance via the blood vessels and its distribution throughout the body. The preferential occurrence of tumors in the genital tract of female mice (carcinomas and sarcomas of the vaginal wall, granulosa cell tumors of the ovaries) points to a possible hormonal involvement; in this context, relevance to prenatally induced tumors in human pathology is discussed. The results emphasize the important role of prenatal carcinogenesis and indicate the increased risk to man by either prenatal initiation or postnatal promotion.