Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

肿瘤微环境中的炎症是癌症的标志，被认为是致癌物的关键特征。然而，直到最近才了解癌症中炎症消退的失败。花生四烯酸和称为类花生酸的相关脂肪酸代谢产物，包括前列腺素、白三烯、脂氧素和环氧类花生酸，严格调节炎症及其消退。炎症的消退现在被认为是一种活跃的生化过程，由内源性专门的促消退脂质自体介质调节，这些介质可以对抗感染并刺激组织修复/再生。环境和化学人类致癌物，包括黄曲霉毒素、石棉、亚硝胺、酒精和烟草，诱发肿瘤促进炎症，并可能破坏炎症的消退，导致毁灭性的全球癌症负担。虽然致癌机制主要集中在诱导突变的基因毒性活动上，但炎症和氧化应激等非基因毒性机制会促进基因毒性、增殖和突变。此外，致癌物引发氧化应激，与炎症和 DNA 损伤协同作用，从而加剧细胞死亡、组织损伤和癌变的恶性反馈循环。相反，刺激炎症消退可以通过巨噬细胞吞噬作用清除细胞碎片和抑制促炎介质的类花生酸/细胞因子风暴来预防癌变。控制宿主炎症反应及其在致癌物诱发癌症中的消退对于降低致癌物诱发的发病率和死亡率至关重要。在这里，我们回顾了最近的证据，即刺激炎症消退，包括促消退脂质介质和可溶性环氧化物水解酶抑制剂，可能是一种新的化学预防方法，可以预防应在人类中评估的致癌物诱发的癌症。