Miura T, Muraoka S, Fujimoto Y, Zhao K
Hokkaido College of Pharmacy, Katsuraoka-cho 7-1, 047-0264, Otaru, Japan.
J Steroid Biochem Mol Biol. 2000 Oct;74(3):93-8. doi: 10.1016/s0960-0760(00)00097-2.
DNA damage induced by estrogens dispersed in liposomes was investigated. 2-Hydroxyestradiol (2HOE(2)) and 4-hydroxyestradiol (4HOE(2)), but not estrone, estradiol-17beta or estriol, caused strand break of plasmid DNA damage in the presence of ADP-Fe(3+). The catechol structure may be necessary for DNA damage. When DNA was incubated with 2HOE(2) for a long time (24 h), DNA damage was induced even at very low concentrations. Adding hydrogen peroxide markedly enhanced the sensitivity of DNA to the attack by 2HOE(2). Hydroxyl radical (HO.) scavengers strongly inhibited the 2HOE(2)-induced DNA damage, and EDTA partially inhibited DNA damage. However, 2HOE(2) caused 8-hydroxyguanine formation from calf thymus DNA only in the presence of EDTA-Fe(3+), but not ADP-Fe(3+). In addition, deoxyribose, which is a detective molecule of HO(.), was not degraded by 2HOE(2) in the presence of ADP-Fe(3+). Upon adding EDTA 2HOE(2) rapidly degraded deoxyribose. These results suggest that DNA strand break caused by 2HOE(2) in the presence of ADP-Fe(3+) was due to ferryl ion rather than HO(.), whereas 8-hydroxyguanine (8HOG) induced by 2HOE(2) in the presence of EDTA-Fe(3+) was due to HO(.).
研究了分散在脂质体中的雌激素诱导的DNA损伤。在存在ADP-Fe(3+)的情况下，2-羟基雌二醇(2HOE(2))和4-羟基雌二醇(4HOE(2))，而不是雌酮、17β-雌二醇或雌三醇，导致质粒DNA损伤的链断裂。儿茶酚结构可能是DNA损伤所必需的。当DNA与2HOE(2)长时间孵育(24小时)时，即使在非常低的浓度下也会诱导DNA损伤。添加过氧化氢显著增强了DNA对2HOE(2)攻击的敏感性。羟基自由基(HO.)清除剂强烈抑制2HOE(2)诱导的DNA损伤，而EDTA部分抑制DNA损伤。然而，2HOE(2)仅在存在EDTA-Fe(3+)的情况下，而不是ADP-Fe(3+)的情况下，导致小牛胸腺DNA形成8-羟基鸟嘌呤。此外，在存在ADP-Fe(3+)的情况下，作为HO(.)检测分子的脱氧核糖不会被2HOE(2)降解。加入EDTA后，2HOE(2)迅速降解脱氧核糖。这些结果表明，在存在ADP-Fe(3+)的情况下，2HOE(2)引起的DNA链断裂是由于铁离子而不是HO(.)，而在存在EDTA-Fe(3+)的情况下，2HOE(2)诱导的8-羟基鸟嘌呤(8HOG)是由于HO(.)。
