Hexavalent chromium [Cr(VI)] is a lung carcinogen and its complete mechanism of action remains to be investigated. Metabolic reprogramming of key energy metabolism pathways (e.g., increased anaerobic glycolysis in the presence of oxygen or "Warburg effect", dysregulated mitochondrial function, and lipogenesis) are important to cancer cell and tumor survival and growth. In our current understanding of Cr(VI)-induced carcinogenesis, the role for metabolic reprogramming remains unclear. In this study, we treated human lung epithelial cells (BEAS-2B) with Cr(VI) for 6 months and obtained malignantly transformed cells from an isolated colony grown in soft agar. We also used Cr(VI)-transformed cells from two other human lung cell lines (BEP2D and WTHBF-6 cells). Overall, we found that all the Cr(VI)-transformed cells had no changes in their mitochondrial respiratory functions (measured by the Seahorse Analyzer) compared with passaged-matched control cells. Using a xenograft tumor growth model, we generated tumors from these transformed cells in Nude mice. Using cells obtained from the xenograft tumor tissues, we observed that these cells had decreased maximal mitochondrial respiration, spare respiratory capacity, and coupling efficiency. These results provide evidence that, although mitochondrial dysfunction does not occur during Cr(VI)-induced transformation of lung cells, it does occur during tumor development.

中文翻译：

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调查在六价铬诱导的肺癌发生过程中线粒体呼吸功能障碍的作用。

六价铬[Cr（VI）]是一种肺致癌物，其完整的作用机理尚待研究。关键能量代谢途径的代谢重编程（例如，在有氧或“ Warburg效应”的情况下增加厌氧性糖酵解，线粒体功能失调和脂肪生成）对癌细胞和肿瘤的存活与生长至关重要。在我们目前对Cr（VI）致癌作用的理解中，对于代谢重编程的作用仍不清楚。在这项研究中，我们用Cr（VI）处理了人肺上皮细胞（BEAS-2B）6个月，并从在软琼脂中生长的分离菌落中获得了恶性转化的细胞。我们还使用了来自其他两个人肺细胞系（BEP2D和WTHBF-6细胞）的Cr（VI）转化细胞。总体，我们发现，与传代匹配的对照细胞相比，所有Cr（VI）转化的细胞的线粒体呼吸功能（由Seahorse Analyzer测量）都没有变化。使用异种移植肿瘤生长模型，我们从裸鼠的这些转化细胞中产生了肿瘤。使用从异种移植肿瘤组织获得的细胞，我们观察到这些细胞具有降低的最大线粒体呼吸，备用呼吸能力和偶联效率。这些结果提供了证据，尽管线粒体功能障碍在Cr（VI）诱导的肺细胞转化过程中没有发生，但在肿瘤发展过程中确实发生。我们从裸鼠的这些转化细胞中产生了肿瘤。使用从异种移植肿瘤组织获得的细胞，我们观察到这些细胞具有降低的最大线粒体呼吸，备用呼吸能力和偶联效率。这些结果提供了证据，尽管线粒体功能障碍在Cr（VI）诱导的肺细胞转化过程中没有发生，但在肿瘤发展过程中确实发生。我们从裸鼠的这些转化细胞中产生了肿瘤。使用从异种移植肿瘤组织获得的细胞，我们观察到这些细胞具有降低的最大线粒体呼吸，备用呼吸能力和偶联效率。这些结果提供了证据，尽管线粒体功能障碍在Cr（VI）诱导的肺细胞转化过程中没有发生，但在肿瘤发展过程中确实发生。