肝癌、結(jié)腸癌或胃癌的最大危險因素之一是病毒或細菌感染引起這些器官的慢性炎癥,。
近日,，一項新的麻省理工學(xué)院的研究為炎癥如何發(fā)生演變成癌癥提供了全面的解釋。
這項研究論文發(fā)表在PNAS雜志上,，這一發(fā)現(xiàn)可能有助于研究人員開發(fā)的方法來預(yù)測慢性炎癥的最終后果,，并設(shè)計藥物來制止這種炎癥。
麻省理工學(xué)院生物工程教授Peter Dedon說：如果你了解其中機制,，那么你就可以設(shè)計出干預(yù)措施,。
在過去的30年中， Tannenbaum帶領(lǐng)一群麻省理工學(xué)院的研究人員致力于研究慢性炎癥和癌癥之間的聯(lián)系,。炎癥是十分常見而又重要的基本病理過程,，體表的外傷感染和各器官的大部分常見病和多發(fā)病都屬于炎癥性疾病。 具有血管系統(tǒng)的活體組織對損傷因子的防御性反應(yīng)稱為炎癥,。
當人體的免疫系統(tǒng)檢測病原體或細胞損傷時,，激活的巨噬細胞和中性粒細胞的大量涌入感染組織入。這些細胞能吞噬細菌,、死細胞和碎片,。
研究人員用H.肝螺桿感染小鼠，在20周后,，小鼠肝臟和結(jié)腸發(fā)生慢性感染,，一些小鼠罹患結(jié)腸癌。在整個20周期間內(nèi),，研究人員測量了大概有十幾個不同類型的DNA,、RNA和蛋白質(zhì)。他們還檢查了組織的損傷情況,，測量哪些基因被開啟和關(guān)閉了,。
在未來的研究中，MIT研究小組計劃更深入更詳細的研究癌癥發(fā)展的機制,，包括某些癌癥細胞為什么會發(fā)生某些類型的DNA損傷,，但某些癌癥細胞不發(fā)生DNA損傷。（生物谷：Bioon.com）
doi:10.1073/pnas.1207829109
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PMID:
Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer
Aswin Mangericha,b, Charles G. Knutsona, Nicola M. Parryc, Sureshkumar Muthupalanic, Wenjie Yea, Erin Prestwicha, Liang Cuia,1, Jose L. McFalinea, et al.
Helicobacter hepaticus-infected Rag2-/- mice emulate many aspects of human inflammatory bowel disease, including the development of colitis and colon cancer. To elucidate mechanisms of inflammation-induced carcinogenesis, we undertook a comprehensive analysis of histopathology, molecular damage, and gene expression changes during disease progression in these mice. Infected mice developed severe colitis and hepatitis by 10 wk post-infection, progressing into colon carcinoma by 20 wk post-infection, with pronounced pathology in the cecum and proximal colon marked by infiltration of neutrophils and macrophages. Transcriptional profiling revealed decreased expression of DNA repair and oxidative stress response genes in colon, but not in liver. Mass spectrometric analysis revealed higher levels of DNA and RNA damage products in liver compared to colon and infection-induced increases in 5-chlorocytosine in DNA and RNA and hypoxanthine in DNA. Paradoxically, infection was associated with decreased levels of DNA etheno adducts. Levels of nucleic acid damage from the same chemical class were strongly correlated in both liver and colon. The results support a model of inflammation-mediated carcinogenesis involving infiltration of phagocytes and generation of reactive species that cause local molecular damage leading to cell dysfunction, mutation, and cell death. There are strong correlations among histopathology, phagocyte infiltration, and damage chemistry that suggest a major role for neutrophils in inflammation-associated cancer progression. Further, paradoxical changes in nucleic acid damage were observed in tissue- and chemistry-specific patterns. The results also reveal features of cell stress response that point to microbial pathophysiology and mechanisms of cell senescence as important mechanistic links to cancer.
