砷酸钠对秀丽线虫生殖细胞周期停滞和细胞凋亡的作用研究

Effect of Arsenate on Germ Cell Cycle Arrest and Apoptosis in Caenorhabditis Elegans

背景与目的:砷在自然界主要以五价砷(AsV)的形式存在,是公认的致癌剂、致畸剂和致突变剂,但其遗传毒性作用机制还不十分清楚,为此,本文研究了砷酸钠对模式生物秀丽隐杆线虫的遗传毒性作用及其机制。材料与方法:分别以0.0、2.5、5.0、10.0和20.0mmol/L砷酸钠处理秀丽隐杆线虫,测定其对线虫平均后代数目、生殖细胞周期和细胞凋亡的影响。结果:在5.0～20.0mmol/L剂量范围内,砷酸钠暴露可导致线虫后代数目降低(P<0.05),在2.5～20.0mmol/L浓度下,砷酸钠可诱导线虫生殖细胞周期停滞和细胞凋亡,并具有显著的时间_剂量效应(P<0.05)。自由基淬灭剂二甲基亚砜(DMSO,0.1%)可抑制砷酸钠诱导的生殖细胞周期停滞,抑制砷酸钠诱导的细胞凋亡。结论:砷酸钠具有遗传毒性作用,可导致线虫生殖细胞凋亡和细胞周期的停滞。

BACKGROUND AND AIM： Inorganic arsenic is a ubiquitous carcinogen, teratogen and mutagen, where it occurs mainly in the pentavalent form in the aquatic environment. The genotoxic effects of arsenate to intact animals are still unclear. In order to understand the potential genotoxic effects of arsenate and the underlying mechanisms, the nematode Caenorhabditis elegans were employed in this study. The studies presented here investigated the effects and the underlying mechanisms of arsenate on the brood size, germ cell cycle arrest and apoptosis of C. elegans. MATERIALS： The C. elegans adult hermaphrodites were exposed to 0.0, 2.5, 5.0, 10.0 or 20.0 mmol/L of arsenate, the brood size, germ cell cycle arrest and apoptosis were assayed after exposure. RESULTS： From arsenate exposure of 5.0 to 20.0 mmol/L, the brood size was significantly smaUer（P 〈0.05）. From the concentrations of 2.5 to 20.0 mmol/L, arsenate exposure caused germ cell cycle arrest and apoptosis in a dose-dependent manner（P 〈 0.05）. Germ cell apoptosis could be detected as early as 6 h after arsenate exposure. The addition of dimethyl sulphoxide （DMSO） could significantly rescue arsenate-induced germ cell cycle arrest and partially reduced apoptosis. CNCLUSION： Arsenate exhibited genotoxic effects, causing germ cell cycle arrest and apoptosis in C. elegans.