Analogs Hamster Embryo Fibroblasts by Diethylstilbestrol and Its Morphological and Neoplastic Transformation of Syrian

A mammalian cell culture system using normal, diploid Syrian hamster embryo fibroblasts was used as a model to study the ability of diethylstilbestrol (DES) and related compounds to induce neoplastic transformation. Like benzo(a)pyrene, a known chemical carcinogen, DES (0.01 to 10 /ig/ml) induces morphological transformation of Syrian hamster embryo fibro blasts in vitro; the transformed colonies were indistinguishable from colonies of benzo(a)pyrene-transformed cells. The mor phologically transformed colonies derived from either benzo(a)pyreneor DES-treated cells were tumorigenic when injected into newborn hamsters. At doses of 0.01 to 1 jttg/ml for 48 hr, DES did not inhibit or stimulate cell proliferation. Structural analogs of DES were also tested in the Syrian hamster embryo transformation system. Like DES, tetrafluorodiethylstilbestrol, dimethylstilbestrol, and c/s,c;s-dienestrol morphologically transformed Syrian hamster embryo cells. The transformation frequency of dimethylstilbestrol was much less than that of DES, tetrafluorodiethylstilbestrol, or c/'s,c/s-dienestrol. Hexestrol, dimethoxydiethylstilbestrol, and frans,frans-dienestrol did not transform these cells. No correlation could be demon strated between reported estrogenic potency of the com pounds and their cell-transforming capacity. Structure-activity relationships developed for these chemicals suggest that me tabolism via specific pathways plays a role in DES-induced cell transformation.