Development of multi-generation assay for endocrine disrupting chemicals

在这项研究中，我们致力于建立一种用于化学品生物评价的多代毒性测试方法。采用线虫线虫秀丽线虫作为模式生物。然后，我们检测了超过五代的亚致死毒性、繁殖力和繁殖力。因此，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线虫繁殖方面具有类胆固醇的效力。相反，睾酮和己烯雌酚抑制线虫的繁殖率。用同样的方法对一些化学物质进行了评价。特别是，即使在1 NM时，双酚A也能显著减少线虫的数量。比较成活的虫卵数量表明，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，我们可以在暴露于雌二醇的线虫提取物中检测到一些磷酸化水平发生变化的蛋白质。这些结果表明，这种毒性检测方法的灵敏度比LC_(50)提高了100-1000倍，自由生活的线虫正在成为检测包括生殖中断在内的化学毒性的有效模式生物。

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.