Estrogen-sensitive Proliferation Pattern of Cloned Syrian Hamster Kidney Tumor Cells¹

Estrogen-sensitive hamster kidney tumor cells H301 and their clonal derivatives were inhibited from proliferating in culture by charcoal-dextran (CD) stripped serum in a dose-dependent manner. Homologous serum was more potent an inhibitor than heterologous (human, bovine, equine) sera. Natural and synthetic estrogens failed to increase the proliferation rate of cells maintained in 2% CD Syrian hamster serum (SHS). At CDSHS concentrations above 2%, cell proliferation was significantly inhibited and estrogens completely reversed this inhibitory effect. Nonestrogenic steroids failed to overcome the serum inhibition. Two synthetic estrogens, moxestrol and 11β-chloromethylestradiol, were 10-fold more potent than estradiol in increasing cell proliferation yields; they were however, less potent than estradiol in inhibiting [³H]estradiol binding to intracellular estrophilins. d-Equilenin, a poor inducer of kidney tumors, was a weak estrogen in the “in culture” proliferation assay. Ethynylestradiol was highly estrogenic in culture while reports suggest that it is a poor tumor inducer in the animal. Progestagens inhibit the growth of estrogen-induced kidney tumors; only promegestone partially blocked the proliferative effect of estradiol in cultures supplemented with 10% CDSHS. Charcoal-dextran stripped serum from animals bearing a diethylstilbestrol implant was as effective as the serum of untreated male hamsters in inhibiting the proliferation of B₃H301 cells. These results are compatible with the following interpretations: (a) hamster serum contains a potent specific inhibitor of the proliferation of estrogen-sensitive cells (estrocolyone); (b) estrogens induce cell proliferation by neutralizing the effect of this serum-borne inhibitor; (c) the poor correlation between estrophilin binding and proliferative potency suggests no direct estrophilin involvement in the proliferative effect of estrogens on these cells; (d) the results obtained in this “in culture” model using estrogen (except ethynylestradiol) and other steroids are compatible with the results obtained in the animal; and (e) the tumorigenic process in Syrian hamster kidneys triggered by estrogens probably involves their direct interaction within these cells (shut-off effect) in addition to the neutralization of the estrocolyone.