Diaplacental carcinogenesis: initiation with the carcinogens dimethylbenzanthracene (DMBA) and urethane during fetal life and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment.

Diaplacental initiation with the carcinogens DMBA or urethane followed by topical treatment of mice of F-1 generation with the tumor promotor TPA led to the formation of benign and malignant tumors on the back skin and also in various internal organs. (This system constitutes a modified 2-stage experiment based on the early schemes of Berenblum and Mottram.) Application of either the carcinogens or the tumor promoter alone did not lead to the formation of tumors within one year. The highest skin papilloma yield was obtained with mice initiated with DMBA from the 16--19th day of fetal life. The highest total tumor yield was obtained after initiation from day 18--21st. The combination urethane/TPA also promoted the formation of tumors of the skin and other organs. The significance of this modified prenatal-postnatal initiation/promotion scheme in human pathology is discussed.