Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA , USA.
Free Radic Res. 2013 Nov;47(11):958-86. doi: 10.3109/10715762.2013.832239. Epub 2013 Oct 4.
The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD)-a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology, and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation.
肠道是一个充满活力和复杂的化学和生物过程相互作用的特殊场所。在这里，包括肠道组织本身、相关免疫系统、肠道微生物群、外源性化学物质和代谢物在内的多种化学和生物系统相互作用，形成了一种复杂而精细调节的组织内稳态。这种内稳态的破坏会导致炎症性肠病（IBD）——一种多因素病因的慢性疾病，与癌症发展风险的增加密切相关。本综述探讨了炎症诱导的结肠癌病因学中化学和生物学机制的最新研究进展。首先概述了在结肠炎症过程中产生的反应性化学物质，然后讨论了炎症的化学和生物学介质之间的机械相互作用、遗传毒理学的作用以及微生物发病机制在疾病发展中的作用。在可能的情况下，我们系统地比较了利用人类 IBD 患者进行的研究和在小鼠中进行的实验研究的证据。这种比较表明，结肠炎相关癌症的小鼠模型与人类的临床相关情况之间存在许多强烈的病理和机制相关性。我们还总结了该领域的几个新出现的问题，如新型炎症相关 DNA 加合物和遗传毒性微生物因素的致癌潜力、炎症诱导的遗传毒性的系统性维度以及这些过程中基因组维持机制的复杂作用。总之，目前的证据表明，化学和生物炎症刺激物会诱导遗传和表观遗传改变，最终导致癌症形成。
