Liu Jing, Wu Sha, Shen Haitao, Cui Jinfeng, Wang Yuan, Xing Lingxiao, Wang Junling, Yan Xia, Zhang Xianghong
Department of Pathology, General Hospital of Chinese People's Armed Police Force, China.
J Toxicol Sci. 2015;40(5):657-65. doi: 10.2131/jts.40.657.
Ochratoxin A (OTA), a toxin produced by several species of Aspergillus and Penicillium, is one of the most abundant food-contaminating mycotoxins. The International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen. Our previous study showed that there were high levels of OTA contaminations in wheat in the areas with high incidence of esophageal cancer in north China. This finding suggests that exposure to low levels of OTA may be a critical etiological factor for esophageal cancer in these areas. However, up to now, the potential biological effects of OTA on human esophageal epithelial cells have not been fully elucidated. In the present study, we explored the cytotoxicity of OTA in human esophageal epithelium immortalized cells (Het-1A). We found that OTA could induce DNA strand breaks and chromosome aberrations in Het-1A cells. OTA-induced DNA damage was followed by G2 cell cycle arrest, and down-regulation of Cdc2 and cyclinB1 contributed to the OTA-induced G2 arrest in Het-1A cells. Additionally, OTA induced apoptosis in Het-1A cells by activating caspase-3. In conclusion, our results indicated that OTA could induce DNA damage, G2 arrest and apoptosis in Het-1A cells, which may be involved in the esophageal toxicity of OTA.
赭曲霉毒素A(OTA)是由几种曲霉属和青霉属真菌产生的一种毒素,是最常见的污染食品的霉菌毒素之一。国际癌症研究机构(IARC)已将OTA归类为可能的人类致癌物。我们之前的研究表明,在中国北方食管癌高发地区的小麦中存在高水平的OTA污染。这一发现表明,接触低水平的OTA可能是这些地区食管癌的一个关键病因。然而,到目前为止,OTA对人食管上皮细胞的潜在生物学效应尚未完全阐明。在本研究中,我们探讨了OTA对人食管上皮永生化细胞(Het-1A)的细胞毒性。我们发现OTA可诱导Het-1A细胞中的DNA链断裂和染色体畸变。OTA诱导的DNA损伤随后导致G2期细胞周期停滞,Cdc2和细胞周期蛋白B1的下调导致OTA诱导的Het-1A细胞G2期停滞。此外,OTA通过激活caspase-3诱导Het-1A细胞凋亡。总之,我们的结果表明,OTA可诱导Het-1A细胞中的DNA损伤、G2期停滞和凋亡,这可能与OTA的食管毒性有关。