Asbestos‐induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species
Asbestos‐induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species
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DOI：
10.1111/pin.13196
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发表时间：
2021-12
影响因子：
2.2
通讯作者：
Yasumasa Okazaki
中科院分区：
文献类型：
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作者：
Yasumasa Okazaki
石棉纤维由于其高耐久性和低生产成本而在世界范围内被用作工业和建筑材料。日本目前禁止石棉的商业使用;然而，石棉诱导的恶性间皮瘤（MM）的风险仍然存在。根据流行病学数据，MM的发病估计发生在初次接触石棉纤维后30-40年的潜伏期之后;因此，MM的持续增加是一个问题。为了使用动物模型探索MM的分子机制，蔗糖铁与铁螯合剂诱导的肉瘤样间皮瘤（SM）通过aCGH和microRNA-199/214的表达微阵列显示了Cdkn 2a/2b纯合缺失的标志。口服地拉罗司铁螯合治疗可降低高级别SM的发生率。此外，在青石棉诱导的MM大鼠中，放血延迟了MM的发展。在二价金属转运蛋白1（Dmt 1）转基因小鼠中，由于活性氧（ROS）的产生较低，MM的发展被延迟。这些结果表明，铁和活性氧在间皮癌发生的重要性。本综述的目的主要集中在细长矿物颗粒（EMP）的发病机制，包括石棉纤维和多壁碳纳米管（MWCNT），除了MM发展的分子机制外，它们具有相似的棒状形状。
Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos‐induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30–40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator‐induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA‐199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high‐grade SM. Moreover, phlebotomy delayed MM development in crocidolite‐induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod‐like shapes in addition to the molecular mechanisms of MM development.