Promotional effect of diethylstilbestrol on human endometrial stromal cells pretreated with a direct-acting carcinogen.
Chronic treatment with 0.1 microM diethylstilbestrol (DES) increased the expression of phenotypic alterations in human endometrial stromal cells pretreated with the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Abnormal morphology, expression of gamma-glutamyltranspeptidase, 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 after 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 cocarcinogen in human cells through a mechanism other than simply stimulating cell proliferation, but that other estrogenic effects may contribute to the promotional process.
D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity*; D004357:Drug Synergism; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D002273:Carcinogens; D007527:Isoenzymes; D008769:Methylnitronitrosoguanidine; D004054:Diethylstilbestrol; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase