Development of multi-generation assay for endocrine disrupting chemicals

在这项研究中，我们研究了开发多代毒性试验的生物评价化学品。采用秀丽隐杆线虫作为模式生物。然后对五代以上的亚致死毒性、繁殖力和繁殖进行了检测。结果表明，秀丽隐杆线虫对脊椎动物的类固醇激素有反应。尤其是雌二醇在支持秀丽隐杆线虫繁殖方面具有类似胆固醇的功效。而睾酮和己烯雌酚抑制秀丽隐杆线虫的繁殖率。用同样的方法对一些化学品进行了评价。特别是在1 nM时，双酚A显著降低秀丽隐杆线虫的数量。对活虫和卵数量的比较表明，酚类物质具有孵化毒性。当我们使用磷酸化氨基酸的特异性抗体进行western-blotting分析时，我们可以检测到雌二醇暴露的秀丽隐杆线虫提取物中磷酸化水平改变的一些蛋白质。结果表明，该方法的灵敏度比lc50高100-1000倍，自由线虫正成为检测化学毒性（包括生殖破坏）的有效模式生物。

In this study, we investigated to develop a multiple-generation toxicity assay for biological evaluation of chemicals. The nematode Caenorhabditis elegans was adopted for a model organism. Then we examined the sublethal toxicity, fecundity and reproduction for over five generations. As the results, C. elegans responds to vertebrate steroid hormones. Especially estradiol has a cholesterol-like potency in supporting the reproduction of C. elegans. In contrast testosterone and diethylstibestrol suppressed the fecundity rate of C. elegans. Some chemicals were evaluated by same method. In particular, bisphenol A was decreased the number of C. elegans significantly even at 1 nM. A comparison of the number of viable worms and eggs suggested that the phenols exert hatching toxicity.When we performed western-blotting analyses using specific antibodies for phosphorylated amino acids, we could detect some proteins which phosphorylation levels were changed in estradiol exposed C. elegans extracts.These results indicated that this toxicity assay had 100-1000-fold higher sensitivity than the LC50s and free living nematode C. elegans is becoming an effective model organism for testing chemical toxicity including reproductive disruption.