The purpose of this application is to perform an experiment testing two alternative mechanisms by which environmentally induced cancer could be transmitted from one generation to the next. The agent inducing cancer is diethylstilbestrol (DES). When mice were exposed to DES transplacentally as fetuses, then raised and bred, their female offspring had a high incidence of reproductive tract tumors. The two possible mechanisms proposed for the second generation tumors are DES-induced mutations of germ cells in the first generation fetus, or DES-induced abnormalities in development of the first generation fetus leading to an abnormal maternal environment for the second generation conceptus. The method proposed to distinguish between these two possibilities is transfer of blastocysts between mice exposed prenatally to DES, or to vehicle. If the second generation tumors arise from germ cell mutation, then the unique reproductive tumors would appear in blastocyst transfer offspring raised by vehicle-exposed mice and derived from DES-exposed germ cells. If the tumors are due to an abnormal maternal environment, then they would appear in offspring raised by DES-exposed mice and derived from unexposed germ cells. This issue is relevant specifically to the several million people exposed prenatally to DES in this country and relevant generally to the problem of transplacental carcinogenesis.
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