Persistent changes in expression of genes involved in inflammation and fibrosis in the lungs of rats exposed to airborne lunar dust

Abstract

NASA is currently planning return missions to the Moon for further exploration and research. The Moon is covered by a layer of potentially reactive fine dust, which could pose a toxicological risk of exposure to explorers. To assess this risk, we exposed rats to lunar dust (LD) that was collected during the Apollo14 mission. Rats were exposed to respirable sizes of LD at concentrations of 0, 2.1, 6.8, 20.8, or 60.6 mg/m³ for 4 weeks. At thirteen  weeks after exposure, we assessed 44,000 gene transcripts and found the expression of 614 genes with known functions were significantly altered in the rats exposed to the 2 higher concentrations of LD, whereas few changes in gene expression were detected in the group exposed to the lowest concentration of LD. Many of the significant changes in gene expression involved genes known to be associated with inflammation or fibrosis. Four genes encoding pro-inflammatory chemokines were analyzed further for all the sampling points at 1 day, and 1, 4, and 13 weeks after the 4-week dust exposure, using real-time polymerase chain reaction. The expression of these genes was altered in a dose- and time-dependent manner and persistently changed in the lungs of the rats exposed to the two higher concentrations of LD. Their expressions are consistent with changes we detected in pulmonary toxicity biomarkers and pathology in these animals during a previous study. Because Apollo-14 LD contains common mineral oxides similar to an Arizona volcanic ash, besides revealing the toxicity of LD, our findings could help elucidate the genomic and molecular mechanisms involved in pulmonary toxicity induced by terrestrial mineral dusts.

Keywords:

• Lunar dust
• moon dust
• pulmonary toxicity
• lunar dust-exposed rats
• gene expression profile
• signaling pathway
• toxicogenomics

Acknowledgements

The lunar dust toxicity studies were funded by the NASA Human Research Program Grant through NASA’s Johnson Space Center and Wyle Bioastronautics Contract #NAS9-02078. This work was conducted through the collaboration of the Bioanalytical Core Laboratory and Toxicology Laboratory at NASA Johnson Space Center. Dr. Ye Zhang was employed as the Senior Scientist of the Bioanalytical Core Laboratory by Wyle Science, Technology & Engineering Group when the work was performed. Part of the manuscript preparation were supported by the NASA Biological and Physical Sciences Division after Dr. Zhang was employed as a Project Scientist at NASA Kennedy Space Center. We greatly thank Kerry George of KBR/Wyle for the in-depth technical review of this manuscript. We highly appreciate the support of Stephanie Bassett and the Animal Care Facility at NASA Johnson Space Center. We also greatly appreciate Drs. Alan Feiveson and Yared Kidane for providing consultation and thank Kyle Williams and Selina Zalesak for their work during their internships.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The lunar dust toxicity studies in rats were funded by the NASA Human Research Program Grant through NASA Johnson Space Center and Wyle Bioastronautics Contract #NAS9-02078. The preparation of the present manuscript was partially supported by NASA Biological and Physical Sciences Division.