Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis.
Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis.
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DOI：
10.1038/sj.bjc.6602664
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发表时间：
2005-08-08
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
我们最近报道了慢性炎症引起的氧化应激增加线粒体DNA （mtDNA）的突变，并可能与癌前状态相关。由于溃疡性结肠炎（UC）患者的结肠黏膜会引发严重的氧化应激，因此研究了炎症性结肠黏膜和结肠炎中mtDNA突变的可能性。结直肠粘膜标本取自伴有或不伴有结肠直肠癌的UC患者和对照组。UC患者结肠粘膜标本中mtDNA突变的频率高于对照组。8-羟基-2 ' -脱氧鸟苷（一种由活性氧引起的DNA加合物）的水平在UC中显著高于对照组。结直肠癌患者的标本中mtDNA突变的数量显著增加。目前的观察结果表明，与慢性炎症相关的结直肠粘膜细胞损伤后的再生导致mtDNA突变的积累。基因（包括mtDNA上的基因）的不稳定性增加，与UC患者结直肠癌的高发病率和多中心发病率是一致的。因此，mtDNA的分析可以为治疗评价提供新的标准，并可能有助于预测癌变风险。
We recently reported that oxidative stress elicited by chronic inflammation increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with precancerous status. Since severe oxidative stress is elicited in the colorectal mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was investigated. Colorectal mucosal specimens were obtained from individuals with UC with and without colitic cancer and from control subjects. The frequency of mtDNA mutations was higher in colorectal mucosal specimens from patients with UC than that from control subjects. The levels of 8-hydroxy-2′-deoxyguanosine, a DNA adduct by reactive oxygen species, were significantly higher in UC than in control. Specimens from patients with colitic cancer contained a significantly higher number of mtDNA mutations. The present observations suggest that the injury followed by the regeneration of colorectal mucosal cells associated with chronic inflammation causes accumulation of mtDNA mutations. The increased instability of genes, including those on the mtDNA, is consistent with the high and multicentric incidence of colorectal cancer in individuals with UC. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation, and may be useful for the prediction of risk of carcinogenesis.
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影响因子：
29.4
作者：
BRENTNALL, TA;CRISPIN, DA;BURMER, GC
通讯作者：
BURMER, GC
影响因子：
3.1
作者：
LASHNER, BA;SILVERSTEIN, MD;HANAUER, SB
通讯作者：
HANAUER, SB
影响因子：
24.5
作者：
SUGITA, A;SACHAR, DB;GREENSTEIN, AJ
通讯作者：
GREENSTEIN, AJ
影响因子：
15.9
作者：
Taylor, RW;Barron, MJ;Turnbull, DM
通讯作者：
Turnbull, DM
影响因子：
56.9
作者：
Fliss, MS;Usadel, H;Sidransky, D
通讯作者：
Sidransky, D