Aflatoxin B₁-Induced Developmental and DNA Damage in Caenorhabditis elegans.

Aflatoxin B₁-Induced Developmental and DNA Damage in Caenorhabditis elegans.
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DOI:
10.3390/toxins9010009
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发表时间:
2016-12-26
期刊:
影响因子:
4.2
通讯作者:
Wang JS
Wang JS
中科院分区:
医学2区
文献类型:
--
作者:
Feng WH;Xue KS;Tang L;Williams PL;Wang JS

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黄曲霉毒素 B1 (AFB1) 是一种普遍存在的霉菌毒素,由有毒的曲霉属物种产生。据报道,AFB1 会对动物和人类的健康造成严重的不良影响,例如癌症以及发育和繁殖异常。 AFB1 也是一种强效基因毒性诱变剂,可在体外和体内引起 DNA 损伤。然而,DNA损伤与异常发育和繁殖之间的联系尚不清楚。为了解决这个问题,我们使用秀丽隐杆线虫作为研究模型,检查了暴露于 AFB1 后的 DNA 损伤、种系细胞凋亡、生长和生殖毒性。结果发现,AFB1诱导DNA损伤和种系细胞凋亡,并以浓度依赖性方式显着抑制线虫的生长和繁殖。与野生型 N2 菌株相比,暴露于 AFB1 能更有效地抑制 DNA 修复缺陷的 xpa-1 线虫的生长或繁殖。根据实时PCR测量的通路相关基因的相对表达水平,发现DNA损伤反应(DDR)通路与AFB1诱导的种系细胞凋亡有关,这进一步在秀丽隐杆线虫的生长和繁殖功能障碍中发挥了重要作用。
Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin produced by toxicogenic Aspergillus species. AFB1 has been reported to cause serious adverse health effects, such as cancers and abnormal development and reproduction, in animals and humans. AFB1 is also a potent genotoxic mutagen that causes DNA damage in vitro and in vivo. However, the link between DNA damage and abnormal development and reproduction is unclear. To address this issue, we examined the DNA damage, germline apoptosis, growth, and reproductive toxicity following exposure to AFB1, using Caenorhabditis elegans as a study model. Results found that AFB1 induced DNA damage and germline apoptosis, and significantly inhibited growth and reproduction of the nematodes in a concentration-dependent manner. Exposure to AFB1 inhibited growth or reproduction more potently in the DNA repair-deficient xpa-1 nematodes than the wild-type N2 strain. According to the relative expression level of pathway-related genes measured by real-time PCR, the DNA damage response (DDR) pathway was found to be associated with AFB1-induced germline apoptosis, which further played an essential role in the dysfunction of growth and reproduction in C. elegans.