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Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume.
Particle and Fibre Toxicology ( IF 7.2 ) Pub Date : 2008-09-08 , DOI: 10.1186/1743-8977-5-12
Patti C Zeidler-Erdely 1 , Michael L Kashon , Lori A Battelli , Shih-Houng Young , Aaron Erdely , Jenny R Roberts , Steven H Reynolds , James M Antonini
Affiliation  

BACKGROUND Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 mug of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 mug soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. RESULTS BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found. CONCLUSION The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.

中文翻译:

暴露于焊接烟雾的肺肿瘤易感 A/J 和抗性 C57BL/6J 小鼠的肺部炎症和肿瘤诱导。

背景焊接烟雾已被归类为对人类“可能致癌”。我们的目标是表征肺部对致癌和非致癌金属焊接烟雾的反应,并确定这些烟雾是否会导致 A/J 小鼠(一种肺肿瘤易感品系)的肺致瘤性增加。我们通过咽部抽吸四次(每 3 天一次)将雄性 A/J 和 C57BL/6J(一种肺肿瘤抗性菌株)暴露于 85 杯气体金属电弧-低碳钢 (GMA-MS)、GMA-不锈钢 (SS ),或手动金属电弧-SS (MMA-SS) 烟雾,或至 25.5 杯可溶性六价铬 (S-Cr)。假手术暴露于盐水载体。在暴露后 2、7 和 28 天进行支气管肺泡灌洗 (BAL)。对于肺肿瘤研究,在暴露后 48 周和 78 周评估 A/J 小鼠的总肿瘤计数和组织病理学变化。结果 BAL 揭示了在暴露于烟雾后炎症反应的程度和分辨率方面存在显着的应变依赖性差异。在 48 周时,含致癌金属的 GMA-SS 烟雾引起肿瘤多样性和发病率的最大增加,但这与假手术没有区别。到 78 周时,GMA-SS 组与假手术组的肿瘤发生率接近显着性(p = 0.057)。发现与假手术组相比,GMA-SS 组的血管周围/支气管周围淋巴浸润显着增加,并且与其他焊接烟雾相比,这种烟雾在肺细胞中的持久性增加。结论 GMA-SS 烟雾的持续性增加与其金属成分相结合可能会引发肺部慢性但温和的炎症状态,可能会增强这种易感小鼠品系的肿瘤发生。
更新日期:2019-11-01
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