ESTROGEN-INDUCED CELL-TRANSFORMATION AND DNA ADDUCT FORMATION IN CULTURED SYRIAN-HAMSTER EMBRYO CELLS

To study the possible involvement of DNA damage in cell transformation induced by estrogens, we examined whether DNA adduct formation is eli cited in cultured Syrian hamster embryo (SHE) cells treated with estro gens and their derivatives by means of the P-32-postlabeling assay. Mo rphological transformation of the cells was induced by treatment with diethylstilbestrol (DES) at 1-10 mu g/mL for 24 h but not by treatment with its derivatives trans, trans-dienestrol (alpha-DIES) or cis, cis -dienestrol (beta-DIES) at 1-10 mu g/mL for 24 h. Similarly, DNA adduc t formation was elicited by exposure of SHE cells to DES at 1-10 mu g/ mL for 24 h but not by either alpha-DIES or beta-DIES. Treatment of SH E cells with DES at 1-10 mu g/mL for 2 h in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant enh anced morphological transformation in a dose-dependent manner. Our pre vious studies have demonstrated that exposure of SHE cells to DES unde r the same conditions with exogenous metabolic activation induces soma tic mutations at the Na+/K+ ATPase locus. Therefore, we examined wheth er with exogenous metabolic activation DES induced DNA adduct formatio n in SHE cells. DNA adducts were not detected when SHE cells were trea ted with DES at 1-10 mu g/mL for 2 h in the presence of exogenous meta bolic activation. Treatment with 17 beta-estradiol (E(2)), 2-hydroxyes tradiol (2-OH E(2)), or 4-hydroxyestradiol (4-OH E(2)) at 1 mu g/mL fo r 24 h induced DNA adduct formation in the cells, in parallel with the induction of cell transformation. The rank order of DNA adduct format ion was 4-OH E(2) > 2-OH E(2) > E(2). The results indicate that estrog ens induce DNA adduct formation in cultured SHE cells, but the inducti on may not be the only mechanism relevant to the initiation of cell tr ansformation. (C) 1996 Wiley-Liss, Inc.