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
11 beta-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 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 diethylstillbestrol 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.