The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University, Misasa, Tottori, 682-0193, Japan.
Bell Land General Hospital, 500-3 Higashiyama, Sakai, Osaka, 599-8247, Japan.
Part Fibre Toxicol. 2023 May 8;20(1):19. doi: 10.1186/s12989-023-00522-0.
Asbestos is a fibrous mineral that was widely used in the past. However, asbestos inhalation is associated with an aggressive type of cancer known as malignant mesothelioma (MM). After inhalation, an iron-rich coat forms around the asbestos fibres, together the coat and fibre are termed an "asbestos ferruginous body" (AFB). AFBs are the main features associated with asbestos-induced MM. Whilst several studies have investigated the external morphology of AFBs, none have characterised the internal morphology. Here, cross-sections of multiple AFBs from two smokers and two non-smokers are compared to investigate the effects of smoking on the onset and growth of AFBs. Morphological and chemical observations of AFBs were undertaken by transmission electron microscopy, energy dispersive x-ray spectroscopy and selected area diffraction.
The AFBs of all patients were composed of concentric layers of 2-line or 6-line ferrihydrite, with small spherical features being observed on the outside of the AFBs and within the cross-sections. The spherical components are of a similar size to Fe-rich inclusions found within macrophages from mice injected with asbestos fibres in a previous study. As such, the spherical components composing the AFBs may result from the deposition of Fe-rich inclusions during frustrated phagocytosis. The AFBs were also variable in terms of their Fe, P and Ca abundances, with some layers recording higher Fe concentrations (dense layers), whilst others lower Fe concentrations (porous layers). Furthermore, smokers were found to have smaller and overall denser AFBs than non-smokers.
The AFBs of smokers and non-smokers show differences in their morphology, indicating they grew in lung environments that experienced disparate conditions. Both the asbestos fibres of smokers and non-smokers were likely subjected to frustrated phagocytosis and accreted mucopolysaccharides, resulting in Fe accumulation and AFB formation. However, smokers' AFBs experienced a more uniform Fe-supply within the lung environment compared to non-smokers, likely due to Fe complexation from cigarette smoke, yielding denser, smaller and more Fe-rich AFBs. Moreover, the lack of any non-ferrihydrite Fe phases in the AFBs may indicate that the ferritin shell was intact, and that ROS may not be the main driver for the onset of MM.
石棉是一种纤维状矿物，过去广泛应用。然而，石棉吸入与一种称为恶性间皮瘤（MM）的侵袭性癌症有关。吸入后，石棉纤维周围形成一层富含铁的涂层，该涂层和纤维一起被称为“石棉铁体”（AFB）。AFB 是与石棉引起的 MM 相关的主要特征。虽然有几项研究调查了 AFB 的外部形态，但没有一项研究描述了其内部形态。在这里，比较了两名吸烟者和两名不吸烟者的多个 AFB 的横截面，以研究吸烟对 AFB 的发生和生长的影响。通过透射电子显微镜、能量色散 X 射线光谱和选区衍射对 AFB 的形态和化学观察进行了研究。
所有患者的 AFB 均由 2 线或 6 线水铁矿的同心层组成，在 AFB 的外部和横截面内观察到小的球形特征。球形成分与之前研究中用石棉纤维注射到小鼠巨噬细胞内发现的富铁内含物大小相似。因此，组成 AFB 的球形成分可能是由于吞噬作用受阻时富铁内含物的沉积所致。AFB 在铁、磷和钙的丰度方面也存在差异，一些层记录的铁浓度较高（致密层），而其他层记录的铁浓度较低（多孔层）。此外，吸烟者的 AFB 比不吸烟者的 AFB 更小且整体更致密。
吸烟者和不吸烟者的 AFB 在形态上存在差异，表明它们在经历不同条件的肺部环境中生长。吸烟者和不吸烟者的石棉纤维都可能经历吞噬作用受阻和黏多糖的积累，导致铁的积累和 AFB 的形成。然而，与不吸烟者相比，吸烟者的 AFB 在肺部环境中经历了更均匀的铁供应，这可能是由于香烟烟雾中铁的络合作用，导致更致密、更小和更富铁的 AFB。此外，AFB 中没有任何非水铁矿铁相的存在可能表明铁蛋白壳是完整的，并且 ROS 可能不是 MM 发生的主要驱动因素。
