Increased oxidative stress has been suggested to initiate and promote tumorigenesis by inducing DNA damage and to suppress tumor development by triggering apoptosis and senescence. The contribution of individual cell types in the tumor microenvironment to these contrasting effects remains poorly understood. We provide evidence that during intestinal tumorigenesis, myeloid cell-derived H₂O₂ triggers genome-wide DNA mutations in intestinal epithelial cells to stimulate invasive growth. Moreover, increased reactive oxygen species (ROS) production in myeloid cells initiates tumor growth in various organs also in the absence of a carcinogen challenge in a paracrine manner. Our data identify an intricate crosstalk between myeloid cell-derived ROS molecules, oxidative DNA damage, and tumor necrosis factor α-mediated signaling to orchestrate a tumor-promoting microenvironment causing invasive cancer.

中文翻译：

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骨髓细胞衍生的活性氧导致上皮诱变。

已经提出增加的氧化应激通过诱导DNA损伤来引发和促进肿瘤发生，并通过触发细胞凋亡和衰老来抑制肿瘤的发展。肿瘤微环境中单个细胞类型对这些对比作用的贡献仍然知之甚少。我们提供的证据表明，在肠道肿瘤发生过程中，髓样细胞衍生的H ₂ O ₂在肠道上皮细胞中触发全基因组DNA突变，以刺激侵袭性生长。此外，在不存在致癌物激发的旁分泌方式下，髓样细胞中增加的活性氧（ROS）产生也会在各个器官中引发肿瘤生长。我们的数据确定了髓细胞来源的ROS分子，氧化性DNA损伤和肿瘤坏死因子α介导的信号之间的错综复杂的串扰，以协调引起肿瘤的微环境。