Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells
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...
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BMC
2022-03-01
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| Series: | BMC Pharmacology and Toxicology |
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| Online Access: | https://doi.org/10.1186/s40360-022-00559-5 |
| _version_ | 1811272142928478208 |
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| author | Hong Lee Sang Hoon Jeong Hyejin Lee Cherry Kim Yoon Jeong Nam Ja Young Kang Myeong Ok Song Jin Young Choi Jaeyoung Kim Eun-Kee Park Yong-Wook Baek Ju-Han Lee |
| author_facet | Hong Lee Sang Hoon Jeong Hyejin Lee Cherry Kim Yoon Jeong Nam Ja Young Kang Myeong Ok Song Jin Young Choi Jaeyoung Kim Eun-Kee Park Yong-Wook Baek Ju-Han Lee |
| author_sort | Hong Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:34:57Z |
| format | Article |
| id | doaj.art-7b72cde22cfb4ed29bcfd790437735e1 |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-04-12T22:34:57Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-7b72cde22cfb4ed29bcfd790437735e12022-12-22T03:13:52ZengBMCBMC Pharmacology and Toxicology2050-65112022-03-0123111510.1186/s40360-022-00559-5Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cellsHong Lee0Sang Hoon Jeong1Hyejin Lee2Cherry Kim3Yoon Jeong Nam4Ja Young Kang5Myeong Ok Song6Jin Young Choi7Jaeyoung Kim8Eun-Kee Park9Yong-Wook Baek10Ju-Han Lee11Medical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineDepartment of Radiology, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineMedical Science Research Center, Ansan Hospital, Korea University College of MedicineDepartment of Medical Humanities and Social Medicine, College of Medicine, Kosin UniversityEnvironmental Health Research Department, Humidifier Disinfectant Health Center, National Institute of Environmental ResearchDepartment of Pathology, Ansan Hospital, Korea University College of MedicineAbstract 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.https://doi.org/10.1186/s40360-022-00559-5Polyhexamethylene guanidine phosphateHumidifier disinfectantHuman pulmonary alveolar epithelial cellsTotal RNA sequencingLung cancer related genes |
| spellingShingle | Hong Lee Sang Hoon Jeong Hyejin Lee Cherry Kim Yoon Jeong Nam Ja Young Kang Myeong Ok Song Jin Young Choi Jaeyoung Kim Eun-Kee Park Yong-Wook Baek Ju-Han Lee Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells BMC Pharmacology and Toxicology Polyhexamethylene guanidine phosphate Humidifier disinfectant Human pulmonary alveolar epithelial cells Total RNA sequencing Lung cancer related genes |
| title | Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells |
| title_full | Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells |
| title_fullStr | Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells |
| title_full_unstemmed | Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells |
| title_short | Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells |
| title_sort | analysis of lung cancer related genetic changes in long term and low dose polyhexamethylene guanidine phosphate phmg p treated human pulmonary alveolar epithelial cells |
| topic | Polyhexamethylene guanidine phosphate Humidifier disinfectant Human pulmonary alveolar epithelial cells Total RNA sequencing Lung cancer related genes |
| url | https://doi.org/10.1186/s40360-022-00559-5 |
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