Nature子刊:抗氧化剂或可用于治疗结肠炎相关结直肠癌
创作:楸楸 审核:EADGBE 2020年05月04日
  • 用大肠杆菌NC101、产肠毒素脆弱拟杆菌、幽门螺杆菌或硫酸葡聚糖钠感染IL10-/-小鼠,引起持续的炎症可诱发8-羟基鸟嘌呤(8-oxoG)DNA损伤;
  • 抗氧化剂(VitC或N-乙酰半胱氨酸)或iNOS抑制剂可减少DNA损伤和肿瘤发生;
  • 在林奇综合征(错配修复缺陷)模型中,菌群产生丁酸可诱导ROS、8-oxoG损伤和双链DNA断裂,该模型中,抗氧化剂可减少DNA损伤但不减少肿瘤发生;
  • IBD患者或可使用抗氧化剂或iNOS抑制剂来减轻氧化DNA损伤。
主编推荐语
EADGBE
慢性炎症可以诱导多种肿瘤的发生。其中,炎症性肠病(IBD)是引发结肠炎相关结直肠癌的最主要风险因素之一,但炎症诱导结肠癌发生的遗传损伤机制尚不清楚。《Nature Communications》近期发表的一项研究表明,由肠道菌群诱导的氧化性DNA损伤是导致炎症性结直肠癌的遗传因素,而抗氧化剂则可抑制这种损伤。该研究为IBD的治疗提供了理论指导。
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Limiting oxidative DNA damage reduces microbe-induced colitis-associated colorectal cancer

限制氧化性DNA损伤可减少由微生物引起的结肠炎相关结直肠癌

10.1038/s41467-020-15549-6

2020-04-14, Article

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Abstract:收起
Inflammatory bowel disease patients have a greatly increased risk of developing colitis-associated colon cancer (CAC); however, the basis for inflammation-induced genetic damage requisite for neoplasia is unclear. Using three models of CAC, we find that sustained inflammation triggers 8-oxoguanine DNA lesions. Strikingly, antioxidants or iNOS inhibitors reduce 8-oxoguanine and polyps in CAC models. Because the mismatch repair (MMR) system repairs 8-oxoguanine and is frequently defective in colorectal cancer (CRC), we test whether 8-oxoguanine mediates oncogenesis in a Lynch syndrome (MMR-deficient) model. We show that microbiota generates an accumulation of 8-oxoguanine lesions in MMR-deficient colons. Accordingly, we find that 8-oxoguanine is elevated in neoplastic tissue of Lynch syndrome patients compared to matched untransformed tissue or non-Lynch syndrome neoplastic tissue. While antioxidants reduce 8-oxoguanine, they do not reduce CRC in Lynch syndrome models. Hence, microbe-induced oxidative/nitrosative DNA damage play causative roles in inflammatory CRC models, but not in Lynch syndrome models.

First Authors:
Thergiory Irrazabal

Correspondence Authors:
Alberto Martin

All Authors:
Thergiory Irrazabal,Bhupesh K Thakur,Mingsong Kang,Yann Malaise,Catherine Streutker,Erin O Y Wong,Julia Copeland,Robert Gryfe,David S Guttman,William W Navarre,Alberto Martin

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