Exacerbation of colitis and promotion of colitis associated cancer by environmental chemicals via modulation of T cell mediated immunity

在这项研究中，一种重要的环境化学物质三丁基锡可能参与了结肠炎的恶化和结肠炎相关性结直肠癌的促进。使用偶氮甲烷和右旋糖胺钠盐诱导的结肠炎和结肠炎相关癌症的小鼠模型，我们发现暴露于环境相关剂量的三丁基锡加剧了结肠炎，并促进了结肠癌的诱导。我们还发现，在肿瘤出现之前，三丁基锡暴露显著增强了Th2细胞因子和下游激活诱导的胞苷脱氨酶的表达，这被称为自然突变因子。另一方面，过量表达内在抗氧化剂硫氧还蛋白的小鼠可以防止诱发结肠癌。此前，我们已经证明三丁基锡通过氧化应激促进Th2细胞分化，从而导致Th2免疫增强。综上所述，这些结果表明，三丁基锡调节Th免疫，导致AID表达增强，参与了结肠炎相关结直肠癌的加重和促进。

In the present study, the possible involvement of a prominent environmental chemical, tributyltin, in the exacerbation of colon inflammation and promotion colitis associated colorectal cancer was examined. Using a mouse model of azoxymethane and dexstran sodium salt induced colitis and colitis associated cancer, we found that exposure of an environmentally relevant dose of tributyltin exacerbated colon inflammation and promoted induction of colon cancer. We also found that the expression Th2 cytokines and downstream activation-induced cytidine deaminase that is know as natural mutator were significantly enhanced by tributyltin exposure before tumor emergence. On the other hand, mouse overexpressing intrinsic anti-oxidant, thioredoxin, was protected from the induction of colon cancer. Previously, we have shown that tributyltin promote Th2 cell differentiation that results in the enhancement of Th2 immunity through oxidative stress. Collectively, these results suggest that modulation of Th immunity by tributyltin that leads to the enhancement of AID expression is involved in the exacerbation of colon inflammation and promotion of colitis associated colorectal cancer.