|Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1988: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1987: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
To study the possible role of gentic damage in the carcinogentic activities of estrogens, Syrian hamster embryo (SHE) cells were treated with estrogens or their metabolites [estrone (E_1), 2-OH-E_1, estradiol (E_2), 2-OH E_2, H-OH-E_2,estriol (E_3) and I-OH-E_3]. The treated cells were assayed for induction of morphological transformation, chromosome aberrations and numerical chromosome changes (i.e., aneuploidy). E_2, 2-OH-E_2 and 4-OH-E_2 induced morphological tranformation of the cells. The frequencies were in the following order: 4-OH-E_2 > 2-OH-E_2 = E_2. No significant increases in the frequencies of morphorogical transformation were observed in cultures treated with E_1, 2-OH-E_1, E_3or 2-OH-E_3. Although E_1, E_2 and E_3 did not cause chromosome aberrations of the cells, their metabolites (2-OH-E_1, 2-OH-E_2, 4-OH-E_2 and 2-OH-E_3) were more toxic and induced a significant level of chromosome aberrations when the cells were treated at high doses. Exposure of cells to E_2, or 4-OH-E_2 resulted in numerical chromosome changes in the near diploid range which correlated with the induction of cell transformation. These results suggest that two types of gentic change may play a role in the induction of cell transformation by estrogens. One involves numerical chromosome changes (aneuploidy) without evident DNA damage, and the other is associated with chromosome aberrations which are induced by estrogen catechol metabolites.