Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells
- Authors
- Lee, Hong; Jeong, Sang Hoon; Lee, Hyejin; Kim, Cherry; Nam, Yoon Jeong; Kang, Ja Young; Song, Myeong Ok; Choi, Jin Young; Kim, Jaeyoung; Park, Eun-Kee; Baek, Yong-Wook; Lee, Ju-Han
- Issue Date
- Mar-2022
- Publisher
- BioMed Central
- Keywords
- Polyhexamethylene guanidine phosphate; Humidifier disinfectant; Human pulmonary alveolar epithelial cells; Total RNA sequencing; Lung cancer related genes
- Citation
- BMC Pharmacology & Toxicology, v.23, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- BMC Pharmacology & Toxicology
- Volume
- 23
- Number
- 1
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/55575
- DOI
- 10.1186/s40360-022-00559-5
- ISSN
- 2050-6511
2050-6511
- Abstract
- Background
Lung injury elicited by respiratory exposure to humidifier disinfectants (HDs) is known as HD-associated lung injury (HDLI). Current elucidation of the molecular mechanisms related to HDLI is mostly restricted to fibrotic and inflammatory lung diseases. In our previous report, we found that lung tumors were caused by intratracheal instillation of polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. However, the lung cancer-related genetic changes concomitant with the development of these lung tumors have not yet been fully defined. We aimed to discover the effect of long-term exposure of PHMG-p on normal human lung alveolar cells.
Methods
We investigated whether PHMG-p could increase distorted homeostasis of oncogenes and tumor-suppressor genes, with long-term and low-dose treatment, in human pulmonary alveolar epithelial cells (HPAEpiCs). Total RNA sequencing was performed with cells continuously treated with PHMG-p and harvested after 35 days.
Results
After PHMG-p treatment, genes with transcriptional expression changes of more than 2.0-fold or less than 0.5-fold were identified. Within 10 days of exposure, 2 protein-coding and 5 non-coding genes were selected, whereas in the group treated for 27–35 days, 24 protein-coding and 5 non-coding genes were identified. Furthermore, in the long-term treatment group, 11 of the 15 upregulated genes and 9 of the 14 downregulated genes were reported as oncogenes and tumor suppressor genes in lung cancer, respectively. We also found that 10 genes of the selected 24 protein-coding genes were clinically significant in lung adenocarcinoma patients.
Conclusions
Our findings demonstrate that long-term exposure of human pulmonary normal alveolar cells to low-dose PHMG-p caused genetic changes, mainly in lung cancer-associated genes, in a time-dependent manner.
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Collections - 2. Clinical Science > Department of Pathology > 1. Journal Articles
- 3. Graduate School > Biomedical Research Center > 1. Journal Articles
- 2. Clinical Science > Department of Radiology > 1. Journal Articles
- 4. Research institute > Cancer Institute > 1. Journal Articles
- 4. Research institute > Research Institute for Skin Image > 1. Journal Articles
- 4. Research institute > Healthcare Readiness Institute for Unified Korea > 1. Journal Articles
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