Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health?
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 C...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024001685 |
| _version_ | 1797253988696981504 |
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| author | Jiawei Hong Keyi Du Hangbiao Jin Yuanchen Chen Yifan Jiang Weichen Zhang Diyu Chen Shusen Zheng Linping Cao |
| author_facet | Jiawei Hong Keyi Du Hangbiao Jin Yuanchen Chen Yifan Jiang Weichen Zhang Diyu Chen Shusen Zheng Linping Cao |
| author_sort | Jiawei Hong |
| collection | DOAJ |
| description | Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 Cl-PFESA as an alternative to PFOS. Although the association between PFAS exposure and hepatocellular carcinoma (HCC) has been demonstrated, the underlying mechanisms that promote HCC proliferation are uncleared. Therefore, we aimed to investigate the effects and differences of PFOS and 6:2 Cl-PFESA on HCC proliferation through in vivo and in vitro tumor models. Our results reveal that both PFOS and 6:2 Cl-PFESA significantly contribute to HCC proliferation in vitro and in vivo. Exposure led to reduced population doubling times, enlarged cell colony sizes, enhanced DNA synthesis efficiency, and a higher proportion of cells undergoing mitosis. Furthermore, both PFOS and 6:2 Cl-PFES) have been shown to activate the PI3K/AKT/mTOR signaling pathway and inhibit necroptosis. This action consequently enhances the proliferation of HCC cells. Our phenotypic assay findings suggest that the tumorigenic potential of 6:2 Cl-PFESA surpasses that of PFOS; in a subcutaneous tumor model using nude mice, the mean tumor weight for the 6:2 Cl-PFESA-treated cohort was 2.33 times that observed in the PFOS cohort (p < 0.01). Despite 6:2 Cl-PFESA being considered a safer substitute for PFOS, the pronounced effects of this chemical on HCC cell growth warrant a thorough assessment of hepatotoxicity risks linked to its usage. |
| first_indexed | 2024-04-24T21:42:49Z |
| format | Article |
| id | doaj.art-a1dd227f82ec41a893e040cbf076499f |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T21:42:49Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-a1dd227f82ec41a893e040cbf076499f2024-03-21T05:35:39ZengElsevierEnvironment International0160-41202024-04-01186108582Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health?Jiawei Hong0Keyi Du1Hangbiao Jin2Yuanchen Chen3Yifan Jiang4Weichen Zhang5Diyu Chen6Shusen Zheng7Linping Cao8Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaKey Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, China; Innovation Research Center of Advanced Environmental Technology, Eco-Industrial Innovation Institute ZJUT, Quzhou, Zhejiang 324400, ChinaKey Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, China; Innovation Research Center of Advanced Environmental Technology, Eco-Industrial Innovation Institute ZJUT, Quzhou, Zhejiang 324400, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Corresponding author at: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 Cl-PFESA as an alternative to PFOS. Although the association between PFAS exposure and hepatocellular carcinoma (HCC) has been demonstrated, the underlying mechanisms that promote HCC proliferation are uncleared. Therefore, we aimed to investigate the effects and differences of PFOS and 6:2 Cl-PFESA on HCC proliferation through in vivo and in vitro tumor models. Our results reveal that both PFOS and 6:2 Cl-PFESA significantly contribute to HCC proliferation in vitro and in vivo. Exposure led to reduced population doubling times, enlarged cell colony sizes, enhanced DNA synthesis efficiency, and a higher proportion of cells undergoing mitosis. Furthermore, both PFOS and 6:2 Cl-PFES) have been shown to activate the PI3K/AKT/mTOR signaling pathway and inhibit necroptosis. This action consequently enhances the proliferation of HCC cells. Our phenotypic assay findings suggest that the tumorigenic potential of 6:2 Cl-PFESA surpasses that of PFOS; in a subcutaneous tumor model using nude mice, the mean tumor weight for the 6:2 Cl-PFESA-treated cohort was 2.33 times that observed in the PFOS cohort (p < 0.01). Despite 6:2 Cl-PFESA being considered a safer substitute for PFOS, the pronounced effects of this chemical on HCC cell growth warrant a thorough assessment of hepatotoxicity risks linked to its usage.http://www.sciencedirect.com/science/article/pii/S0160412024001685PFOS6:2 Cl-PFESAHepatocellular CarcinomaPI3K/AKT/mTOR pathwayNecroptosis |
| spellingShingle | Jiawei Hong Keyi Du Hangbiao Jin Yuanchen Chen Yifan Jiang Weichen Zhang Diyu Chen Shusen Zheng Linping Cao Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? Environment International PFOS 6:2 Cl-PFESA Hepatocellular Carcinoma PI3K/AKT/mTOR pathway Necroptosis |
| title | Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? |
| title_full | Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? |
| title_fullStr | Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? |
| title_full_unstemmed | Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? |
| title_short | Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health? |
| title_sort | evidence of promoting effects of 6 2 cl pfesa on hepatocellular carcinoma proliferation in humans an ideal alternative for pfos in terms of environmental health |
| topic | PFOS 6:2 Cl-PFESA Hepatocellular Carcinoma PI3K/AKT/mTOR pathway Necroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024001685 |
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