Hexavalent chromium exposure impacts the metabolome of human lung fibroblast cells

Abstract

Introduction

Lung cancer is the number one cause of cancer death and survival rates have not significantly improved for decades. The underlying mechanism of lung cancer remains elusive, but it is known chromosome instability, altered DNA, and dysregulated cellular energetics are key to cancers. However, the importance of energetics during chemical carcinogenesis is unexplored.

Methods

We exposed human lung cells to hexavalent chromium [Cr(VI)], a known human respiratory carcinogen, for 24 or 120 h. Then, we performed untargeted metabolomics and analyzed changes with concentration and time through differential metabolomics.

Results

There was a distinct metabolic response with increasing Cr(VI) concentrations and a difference in the metabolic response with time, where metabolic enrichment of amino acid metabolism and nucleotide metabolism were affected with time and Cr(VI) treatment.

Conclusions

This study provides the first link between energy metabolism responses and chemical carcinogenesis, providing the foundation for a more in-depth investigation into how Cr(VI) alters the metabolic response of cells to induce lung cancer. We anticipate our study will be a starting point for more in-depth investigations into the role of dysregulated cellular energetics during carcinogenesis, which will further establish these changes as a critical early-stage event in carcinogenesis.