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Long-term hexavalent chromium exposure facilitates colorectal cancer in mice associated with changes in gut microbiota composition
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-03-04 , DOI: 10.1016/j.fct.2020.111237
Zecai Zhang , Hongyang Cao , Ning Song , Lixiao Zhang , Yongguo Cao , Jiandong Tai

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Hexavalent chromium [Cr(VI)] is often present in groundwater. Chronic Cr(VI) exposure is suggested to be one of the main factors inducing cancer. However, the correlation between Cr(VI) and CRC remains unclear. In this study, we investigated the role of Cr(VI) in CRC by establishing a mouse CRC model induced by 1, 2-dimethylhydrazine (DMH). The results showed that Cr(VI) increased weight loss in DMH-induced mice and promoted the formation of tumors. Cr(VI) also increased DMH-induced proliferating cell nuclear antigen (PCNA) levels. Investigation of the underlying mechanisms found that Cr(VI) significantly decreased DMH-induced SOD, GSH and CAT levels, while, the MDA level increased. Metagenomic analyses found that the abundance of Firmicutes and Bacteroidetes in the DMH + Cr group was down-regulated. Interestingly, the combination of Cr(VI) and DMH significantly increased the abundance of Verrucomicrobia. At the family and genus levels, families Akkermansiaceae and Saccharimonadaceae and genus Akkermansia were more abundant in the DMH + Cr group, whereas the abundance of short-chain fatty acid (SCFA)-producing bacteria (family Muribaculaceae, family Lachnosipiraceae, genus Lachnospiraceae_NK4A136_group, and genus Roseburia) decreased. These results indicate that Cr(VI) might aggravate CRC by altering the composition of the gut microflora.



中文翻译:

长期六价铬暴露可促进与肠道菌群组成相关的小鼠结直肠癌

大肠癌(CRC)是全球范围内与癌症相关的死亡率的主要原因之一。地下水中经常存在六价铬[Cr(VI)]。慢性六价铬暴露被认为是诱发癌症的主要因素之一。但是,Cr(VI)与CRC之间的相关性仍不清楚。在这项研究中,我们通过建立由1,2-二甲基肼(DMH)诱导的小鼠CRC模型,研究了Cr(VI)在CRC中的作用。结果表明,Cr(VI)增加了DMH诱导的小鼠的体重减轻,并促进了肿瘤的形成。六价铬也增加了DMH诱导的增殖细胞核抗原(PCNA)的水平。对潜在机理的研究发现,Cr(VI)显着降低DMH诱导的SOD,GSH和CAT水平,而MDA水平升高。元基因组学分析发现DMH + Cr组的硬毛虫拟杆菌属被下调。有趣的是,Cr(VI)和DMH的组合显着增加了Verrucomicrobia的丰度。在家庭和属水平,家庭AkkermansiaceaeSaccharimonadaceae和属Akkermansia是在DMH +的Cr组中更丰富,而丰度的短链脂肪酸的(SCFA)产生细菌(家庭Muribaculaceae,家庭Lachnosipiraceae,属毛螺_NK4A136_group,和属罗斯氏)减少。这些结果表明Cr(VI)可能会通过改变肠道菌群的组成而加重CRC。

更新日期:2020-03-04
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