Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Sydney Medical School, The University of Sydney, NSW, Australia.
Free Radic Biol Med. 2019 Mar;133:206-215. doi: 10.1016/j.freeradbiomed.2018.10.401. Epub 2018 Oct 10.
Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.
癌症是大多数国家人类死亡的主要原因。随着各种医学治疗方法的进步，这种趋势有所增加，这表明尽管最终结果可能会受到暴露组和统计学的影响，但我们无法逃避癌变。癌症根据其细胞分化进行分类。间皮细胞的特点是它们排列在体腔中，促进器官的平滑运动，但不暴露于外部环境。恶性间皮瘤，简称间皮瘤，要么发生在胸膜、腹膜或心包腔中，要么发生在睾丸鞘膜腔中。间皮瘤是一种相对罕见的癌症，但由于与石棉暴露有关，而石棉暴露是现代工业发展造成的，因此具有重要的社会意义。主要的发病机制包括氧化应激，要么是通过催化反应对抗石棉表面，要么是巨噬细胞吞噬作用受阻，以及在吞噬活性存在的情况下，石棉纤维对血红蛋白和组蛋白的特异性吸附。直径约为 50nm 的多壁碳纳米管，另外还吸附转铁蛋白，对啮齿动物的间皮细胞具有类似的致癌性，因此被归类为 2B 组致癌物。人类和大鼠间皮瘤中发现的遗传改变显著包含在其他过量铁诱导的致癌模型中发现的改变。放血和铁螯合疗法已成功预防大鼠间皮瘤。或者，将非热等离子体加载到间皮瘤细胞中会导致铁死亡。因此，外来纤维状无机材料的致癌作用可能与生命诞生及其进化的未被揭示的分子机制重叠。
