Estrogen-sensitive proliferation pattern of cloned Syrian hamster kidney tumor cells.
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.
Soto
A M
AM
Tufts University School of Medicine, Department of Anatomy and Cellular Biology, Boston, Massachusetts 02111.
Bass
J C
JC
Sonnenschein
C
C
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D006224:Cricetinae; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology*; D008647:Mesocricetus; D011397:Promegestone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000502:physiology; D013256:Steroids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D003470:Culture Media; D004967:Estrogens; D011960:Receptors, Estrogen; D013256:Steroids; C010140:estrophilin; D004958:Estradiol; D011397:Promegestone