Di Giuseppe Dario, Scarfì Sonia, Alessandrini Andrea, Bassi Anna Maria, Mirata Serena, Almonti Vanessa, Ragazzini Gregorio, Mescola Andrea, Filaferro Monica, Avallone Rossella, Vitale Giovanni, Scognamiglio Valentina, Gualtieri Alessandro F
Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Italy; Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Pisa, Italy.
Toxicology. 2022 Jan 30;466:153081. doi: 10.1016/j.tox.2021.153081. Epub 2021 Dec 22.
Inhalation of mineral fibres is associated with the onset of an inflammatory activity in the lungs and the pleura responsible for the development of fatal malignancies. It is known that cell damage is a necessary step for triggering the inflammatory response. However, the mechanisms by which mineral fibres exert cytotoxic activity are not fully understood. In this work, the kinetics of the early cytotoxicity mechanisms of three mineral fibres (i.e., chrysotile, crocidolite and fibrous erionite) classified as carcinogenic by the International Agency for Research on Cancer, was determined for the first time in a comparative manner using time-lapse video microscopy coupled with in vitro assays. All tests were performed using the THP-1 cell line, differentiated into M0 macrophages (M0-THP-1) and exposed for short times (8 h) to 25 μg/mL aliquots of chrysotile, crocidolite and fibrous erionite. The toxic action of fibrous erionite on M0-THP-1 cells is manifested since the early steps (2 h) of the experiment while the cytotoxicity of crocidolite and chrysotile gradually increases during the time span of the experiment. Chrysotile and crocidolite prompt cell death mainly via apoptosis, while erionite exposure is also probably associated to a necrotic-like effect. The potential mechanisms underlying these different toxicity behaviours are discussed in the light of the different morphological, and chemical-physical properties of the three fibres.
吸入矿物纤维与肺部和胸膜的炎症活动发作有关，而这种炎症活动是导致致命恶性肿瘤发展的原因。已知细胞损伤是引发炎症反应的必要步骤。然而，矿物纤维发挥细胞毒性作用的机制尚未完全了解。在这项工作中，首次以比较的方式，使用延时视频显微镜结合体外试验，测定了国际癌症研究机构列为致癌物质的三种矿物纤维（即温石棉、青石棉和纤维状毛沸石）早期细胞毒性机制的动力学。所有测试均使用THP-1细胞系，将其分化为M0巨噬细胞（M0-THP-1），并短时间（8小时）暴露于25μg/mL的温石棉、青石棉和纤维状毛沸石等分试样中。纤维状毛沸石对M0-THP-1细胞的毒性作用在实验的早期阶段（2小时）就已显现，而青石棉和温石棉的细胞毒性在实验期间逐渐增加。温石棉和青石棉主要通过凋亡促使细胞死亡，而暴露于毛沸石可能还与类似坏死的效应有关。根据这三种纤维不同的形态、化学物理性质，讨论了这些不同毒性行为背后的潜在机制。
