The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53+/-) mice has not been investigated. We hypothesized that p53+/- mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53+/+) or p53+/- mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53+/+ or p53+/- mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53+/- and p53+/+ mice. A constitutively larger area of CD45R+/CD3+ lymphoid tissue was observed in p53+/- mice compared to p53+/+ mice. Importantly, p53+/- mice had larger granulomas induced by rMWCNTs as compared to p53+/+ mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.

中文翻译：

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p53在对缠结或棒状多壁碳纳米管的慢性肺免疫反应中的作用。

多壁碳纳米管（MWCNT）的纤维状形状让人联想到石棉，表明它们在吸入时会造成类似的健康危害，包括肺纤维化和间皮瘤。缺乏肿瘤抑制因子p53的小鼠容易发生癌变。但是，尚未研究传递到p53杂合（p53 +/-）小鼠肺部的MWCNT的慢性病理作用。我们假设p53 +/-小鼠在暴露于缠结（t-）或棒状（r-）MWCNTs之后将很容易患上肺部肿瘤。在连续四周内每周通过口咽抽吸将野生型（p53 + / +）或p53 +/-小鼠暴露于MWCNT（1 mg / kg），并在首次暴露后11个月评估细胞和病理结果。在暴露于t-或rMWCNT的p53 + / +或p53 +/-小鼠中未观察到肺或胸膜肿瘤。与tMWCNTs相比，rMWCNTs在p53 +/-和p53 + / +小鼠的终末细支气管中诱导了较大的肉芽肿，大量的淋巴样聚集物和更大的上皮细胞增生。与p53 + / +小鼠相比，在p53 +/-小鼠中观察到CD45R + / CD3 +淋巴组织的组成性更大区域。重要的是，与p53 + / +小鼠相比，p53 +/-小鼠具有更大的rMWCNTs诱导的肉芽肿。这些发现表明，p53缺陷和包括纳米管几何形状在内的物理化学特征的组合是易受MWCNT诱导的淋巴样浸润和肉芽肿形成的因素。在p53 +/-和p53 + / +小鼠的末端细支气管中，淋巴样聚集物的数量增加，上皮细胞增生。与p53 + / +小鼠相比，在p53 +/-小鼠中观察到CD45R + / CD3 +淋巴组织的组成性更大区域。重要的是，与p53 + / +小鼠相比，p53 +/-小鼠具有更大的rMWCNTs诱导的肉芽肿。这些发现表明，p53缺陷和包括纳米管几何形状在内的物理化学特征的组合是易受MWCNT诱导的淋巴样浸润和肉芽肿形成的因素。在p53 +/-和p53 + / +小鼠的末端细支气管中，淋巴样聚集物的数量增加，上皮细胞增生的现象也增加。与p53 + / +小鼠相比，在p53 +/-小鼠中观察到CD45R + / CD3 +淋巴组织的组成性更大区域。重要的是，与p53 + / +小鼠相比，p53 +/-小鼠具有更大的rMWCNTs诱导的肉芽肿。这些发现表明，p53缺陷和包括纳米管几何形状在内的物理化学特征的组合是易受MWCNT诱导的淋巴样浸润和肉芽肿形成的因素。与p53 + / +小鼠相比，p53 +/-小鼠具有更大的rMWCNTs诱导的肉芽肿。这些发现表明，p53缺乏和包括纳米管几何形状在内的物理化学特征的组合是易受MWCNT诱导的淋巴样浸润和肉芽肿形成的因素。与p53 + / +小鼠相比，p53 +/-小鼠具有更大的rMWCNTs诱导的肉芽肿。这些发现表明，p53缺陷和包括纳米管几何形状在内的物理化学特征的组合是易受MWCNT诱导的淋巴样浸润和肉芽肿形成的因素。