Chronic treatment with 0.1 μM diethylstilbestrol (DES) increased the expression of phenotypic alterations in human endometriaJ stromal cells pretreated with the direct-acting carcinogen N-methyl-N' -nitro-N-nitrosoguanidine (MNNG). Abnormal morphology, expression of gamma-glutamyltrans-peptidase, and the ability to form colonies under restrictive conditions were more pronounced after combined treatment with carcinogen and DES compared to carcinogen or DES alone. This effect did not appear to be due simply to growth enhancement by DES, because acute treatment with DES did not alter colony formation, growth rate or thymidine incorporation into DNA in stromal cell cultures. Neither did the presence of DES alter the toxicity of MNNG. DES did cause shifts in the isoenzyme distribution of lactate dehydrogenase which could be indicative of a hormonal response. The results suggest that DES may act as a tumor promoter or cocar-cinogen in human cells through a mechanism other than simply stimulating cell proliferation, but that other estrogenic effects may contribute to the promotional process.
Bibliographical noteFunding Information:
The authors thank Ms. Amanda Wright Durrill for manuscript preparation and Dr. Marc Mass for helpful discussions. Supported by National Research Service Awards CA09156 from the National Cancer Institute (J.M.S.) and ES07017 from the National Institute for Environmental Health Sciences (K.G.N.), research career development award CAOO431 (D.G.K.), and Grant CA31733 (D.G.K.) from the National Cancer Institute.