Toxic effects of realgar transforming solution on the reproduction of Caenorhabditis elegans

Toxic effects of realgar transforming solution on the reproduction of Caenorhabditis elegans
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雄黄转化液对秀丽隐杆线虫繁殖的毒性作用

DOI:
10.1080/02772248.2017.1387264
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发表时间:
2018-01
影响因子:
1.8
通讯作者:
Li Hongyu
Li Hongyu
中科院分区:
环境科学与生态学4区
文献类型:
--
作者:
Liu Dongling;Zhi Dejuan;Wang Mengqi;Bai Yanli;Gao Chunhong;Gao Jiangli;Tian Jing;Wang Dong;Li Hongyu

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雄黄转化液是一种砷制剂,在体内外均表现出低毒性的抗癌作用。本研究以秀丽隐杆线虫为材料,对其生殖毒性进行了评价,并探讨了其可能的作用机制。雄黄转化液仅在37.5mg/L时能显著降低N2和let-60 ras(gf)突变体蠕虫的产卵量,并诱导其增殖停滞和凋亡;而三氧化二砷则能显著降低N2和let-60 ras(gf)突变体蠕虫的产卵量,并诱导其增殖停滞和凋亡。丝裂原活化蛋白激酶和蛋白p53途径可能参与生殖毒性,如实时定量聚合酶链反应、RNA干扰和丝裂原活化蛋白激酶和p53抑制实验所证明。结果表明,雄黄转化液在低砷浓度下的生殖毒性低于三氧化二砷,其生殖毒性的分子机制可能与三氧化二砷不同。
ABSTRACT Realgar transforming solution is an arsenic formulation which has shown anticancer effects with low toxicity both in vivo and in vitro. In this study, Caenorhabditis elegans was used to evaluate its reproductive toxicity and its possible mechanisms. Realgar transforming solution decreased the brood size and induced proliferation arrest and apoptosis significantly only at an elemental concentration of 37.5 mg/L, while arsenic trioxide reduced the brood sizes and induced proliferation arrest and apoptosis of both the wild type N2 and let-60 ras(gf) mutant worms in an arsenic concentration dependent manner. Mitogen-activated protein kinase and protein p53 pathways may be involved in reproductive toxicity as evidenced by real-time quantitative polymerase chain reaction, RNA interference, and inhibition experiments with mitogen-activated protein kinases and p53. In conclusion, realgar transforming solution at the low arsenic (As) concentrations showed lower reproductive toxicity than arsenic trioxide, and a different molecular mechanism of reproductive toxicity is suggested.
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