DNA Damage and Toxicogenomic Analyses of Hydrogen Sulfide in Human Intestinal Epithelial FHs 74 Int Cells
DNA Damage and Toxicogenomic Analyses of Hydrogen Sulfide in Human Intestinal Epithelial FHs 74 Int Cells
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DOI：
10.1002/em.20546
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发表时间：
2010-05-01
影响因子：
2.8
通讯作者：
Gaskins, H. Rex
中科院分区：
文献类型：
--
作者：
Attene-Ramos, Matias S.;Nava, Gerardo M.;Gaskins, H. Rex
硫化氢（H2S）是硫酸盐还原细菌的一种代谢终产物，对结肠上皮具有遗传毒性，也可能与溃疡性结肠炎和结直肠癌等慢性疾病有关。该研究定义了未转化的人肠上皮细胞（FHs 74 Int）对H2S的早期（30分钟）和晚期（4小时）反应。采用单细胞凝胶电泳（comet）法测定H2S的遗传毒性。使用途径特异性定量RT-PCR基因阵列分析暴露于具有基因毒性而非细胞毒性浓度的H2S （500 μ M H2S）后基因表达的变化。H2S在250 ~ 2000 μ M的浓度范围内具有遗传毒性，这与大肠中的浓度相似。基因表达在4小时时发生显著变化，PTGS2 （COX-2，上调7.92倍）和WNT2（下调7.08倍）的反应最大。COX-2是唯一在30分钟和4小时均上调的基因。总体而言，该研究表明H2S调节参与细胞周期进程的基因表达，并引发炎症和DNA修复反应。本研究证实了H2S在未转化的人肠上皮细胞中的遗传毒性，并确定了这种细菌代谢物可能扰乱细胞稳态并导致慢性肠道疾病发病的功能途径。环绕。中国生物工程学报，2010,31(1):394 - 394。(C) 2010 Wiley-Liss, Inc。
Hydrogen sulfide (H2S), a metabolic end product of sulfate-reducing bacteria, represents a genotoxic insult to the colonic epithelium, which may also be linked with chronic disorders such as ulcerative colitis and colorectal cancer. This study defined the early (30 min) and late (4 hr) response of nontransformed human intestinal epithelial cells (FHs 74 Int) to H2S. The genotoxicity of H2S was measured using the single-cell gel electrophoresis (comet) assay. Changes in gene expression were analyzed after exposure to a genotoxic, but not cytotoxic, concentration of H2S (500 mu M H2S) using pathway-specific quantitative RT-PCR gene arrays. H2S was genotoxic in a concentration range from 250 to 2,000 mu M, which is similar to concentrations found in the large intestine. Significant changes in gene expression were predominantly observed at 4 hr, with the greatest responses by PTGS2 (COX-2; 7.92-fold upregulated) and WNT2 (7.08-fold downregulated). COX-2 was the only gene upregulated at both 30 min and 4 hr. Overall, the study demonstrates that H2S modulates the expression of genes involved in cell-cycle progression and triggers both inflammatory and DNA repair responses. This study confirms the genotoxic properties of H2S in nontransformed human intestinal epithelial cells and identifies functional pathways by which this bacterial metabolite may perturb cellular homeostasis and contribute to the onset of chronic intestinal disorders. Environ. Mol. Mutagen. 51:304-314, 2010. (C) 2010 Wiley-Liss, Inc.