Details:

Alternative Title:
Inhal Toxicol
Personal Author:
Sager, Tina M. ; Umbright, Christina M. ; Mustafa, Gul Mehnaz ; Roberts, Jenny R. ; Orandle, Marlene S. ; ... More +
Sager, Tina M. ; Umbright, Christina M. ; Mustafa, Gul Mehnaz ; Roberts, Jenny R. ; Orandle, Marlene S. ; Cumpston, Jared L. ; McKinney, Walter G. ; Boots, Theresa ; Kashon, Michael L. ; Joseph, Pius Less -
Description:
Purpose:

To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7).

Materials and methods:

Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT-7 particles at target cumulative doses (concentration × time) ranging from 22.5 to 180 (mg/m3)h over a three-day (6 hours/day) period and toxicity and global gene expression profiles were determined in the lungs.

Results:

MWCNT-7 particles, associated with alveolar macrophages (AMs), were detected in rat lungs following the exposure. Mild to moderate lung pathological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and polymorphonuclear leukocytes (PMNs), intracellular oxidant generation by phagocytes, and levels of cytokines were significantly (p < 0.05) increased in response to exposure to MWCNT-7. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in all the MWCNT-7 exposed rats. Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure.

Conclusions:

Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7.


Subjects:
[+]
Animals Article Bronchoalveolar Lavage Fluid Fibrosis Gene Expression Inflammation Inhalation Exposure Lung Lung Toxicity Molecular Mechanisms Multi-walled Carbon Nanotubes Nanotubes, Carbon Rats
Source:
Inhal Toxicol. 34(7-8):200-218
Pubmed ID:
35648795
Pubmed Central ID:
PMC9885491
Document Type:
Journal Article
Funding:
CC999999/ImCDC/Intramural CDC HHSUnited States/
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:1a3219aa9e60412dc9163ee29edef813681200ac14d763f47f7080b441312904
Download URL:
https://stacks.cdc.gov/view/cdc/124153/cdc_124153_DS1.pdf
File Type:

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