Hiraku Yusuke
Department of Environmental Health, University of Fukui School of Medical Science, Eiheiji, Fukui, Japan.
J Occup Health. 2025 Jan 7;67(1). doi: 10.1093/joccuh/uiaf003.
Many chemicals have been used for industrial purposes, and some of them are carcinogenic to humans. However, the molecular mechanisms of their carcinogenetic effects have not been well understood. Reactive oxygen species are generated from industrial chemicals and contribute to carcinogenesis. Particles and fibers are accumulated in respiratory systems by inhalation exposure and cause chronic inflammation. Under inflammatory conditions, reactive nitrogen species are generated from inflammatory and epithelial cells. These species cause oxidative and nitrative DNA damage, leading to carcinogenesis. We carried out experiments on DNA damage induced by various industrial chemicals and investigated their molecular mechanisms.
We examined oxidative DNA damage induced by industrial chemicals using DNA fragments derived from human cancer-relevant genes by polyacrylamide gel electrophoresis. Using immunohistochemistry and immunocytochemistry we also examined the formation of 8-nitroguanine (8-nitroG), a DNA lesion formed under inflammatory conditions, in lung tissues and cultured cells exposed to industrial chemicals.
Benzene and o-toluidine metabolites caused oxidative damage to DNA fragments in the presence of Cu(II). H2O2 and Cu(I) were generated during oxidation of these chemicals and involved in DNA damage. 8-NitroG formation was observed in lung tissues of asbestos-exposed mice and humans. Carbon nanomaterials and indium compounds induced 8-nitroG formation in human lung epithelial cells via the release of damage-associated molecular patterns from exposed cells.
Various industrial chemicals are considered to induce carcinogenesis by causing oxidative and nitrative DNA damage. These findings provide an insight into risk assessment of industrial chemicals and prevention of carcinogenesis in workplaces.
许多化学物质已被用于工业目的，其中一些对人类具有致癌性。然而，它们致癌作用的分子机制尚未得到充分了解。工业化学品会产生活性氧物种，促进癌症发生。颗粒和纤维通过吸入暴露在呼吸系统中积累并引起慢性炎症。在炎症条件下，炎症细胞和上皮细胞会产生活性氮物种。这些物质会导致氧化性和硝化性DNA损伤，从而引发癌症。我们对各种工业化学品诱导的DNA损伤进行了实验，并研究了其分子机制。
我们使用来自人类癌症相关基因的DNA片段，通过聚丙烯酰胺凝胶电泳检测工业化学品诱导的氧化性DNA损伤。我们还使用免疫组织化学和免疫细胞化学方法，检测了暴露于工业化学品的肺组织和培养细胞中8-硝基鸟嘌呤（8-nitroG）的形成，8-nitroG是在炎症条件下形成的一种DNA损伤。
苯和邻甲苯胺代谢物在铜（II）存在的情况下对DNA片段造成氧化性损伤。这些化学物质氧化过程中产生了过氧化氢和铜（I），并参与了DNA损伤。在接触石棉的小鼠和人类的肺组织中观察到了8-nitroG的形成。碳纳米材料和铟化合物通过暴露细胞释放损伤相关分子模式，诱导人肺上皮细胞中8-nitroG的形成。
各种工业化学品被认为通过造成氧化性和硝化性DNA损伤来诱导癌症发生。这些发现为工业化学品的风险评估和工作场所癌症预防提供了见解。
