Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds
Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds
复制标题
DOI：
10.1093/toxsci/kfi074
复制
发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Ohta, S
中科院分区：
文献类型：
--
作者：
Kitamura, S;Suzuki, T;Ohta, S
采用不同的体内外实验方法，对双酚A(BPA)及其相关的19种化合物的内分泌干扰活性进行了比较研究。双酚A及其相关化合物对人乳腺癌细胞株MCF-7具有类雌激素活性，但活性存在显著差异。四氯双酚A(TCBPA)活性最高，其次是双酚B、双酚A和四甲基双酚A(TMBPA)，2，2-二(4-羟基苯基)-1-丙醇、1，1-二(4-羟基苯基)丙酸和2，2-二苯丙烷活性很低或没有活性。观察了TMBPA和四溴双酚A(TBBPA)对17β-雌二醇的抗雌激素活性。TCBPA、TBBPA和BPA在去卵巢小鼠体内子宫滋养试验中呈阳性反应。相反，双酚A及其相关化合物对5α-二氢睾酮在小鼠成纤维细胞系NIH3T3中的雄激素生成活性有明显的抑制作用。TMBPA的拮抗活性最强，其次是双酚AF、双酚AD、双酚B和双酚A。而TBBPA、TCBPA和2，2-二苯基丙烷则没有活性。TBBPA、TCBPA、TMBPA和3，3‘-二甲基双酚A对大鼠垂体细胞系GH3具有显著的甲状腺激素活性，后者以甲状腺激素依赖的方式释放生长激素。然而，BPA和其他衍生品并没有表现出这样的活动。结果表明，BPA衍生物的A-苯环和B-苯环上的4-羟基是这些激素活性所必需的，苯环上3，5-位的取代基和桥链上的取代基对活性有显著影响。
The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA, and tetramethylbisphenol A (TMBPA); 2,2-bis(4-hydroxyphenyl)-1-propanol, 1,1-bis(4-hydroxyphenyl)propionic acid and 2,2-diphenylpropane showed little or no activity. Anti-estrogenic activity against 17 beta-estradiol was observed with TMBPA and tetrabromobisphenol A (TBBPA). TCBPA, TBBPA, and BPA gave positive responses in the in vivo uterotrophic assay using ovariectomized mice. In contrast, BPA and some related compounds showed significant inhibitory effects on the androgenic activity of 5 alpha-dihydrotestosterone in mouse fibroblast cell line NIH3T3. TMBPA showed the highest antagonistic activity, followed by bisphenol AF, bisphenol AD, bisphenol B, and BPA. However, TBBPA, TCBPA, and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA, and 3,3'-dimethylbisphenol A exhibited significant thyroid hormonal activity towards rat pituitary cell line GH3, which releases growth hormone in a thyroid hormone-dependent manner. However, BPA and other derivatives did not show such activity. The results suggest that the 4-hydroxyl group of the A-phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.