Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) induce epigenetic alterations and promote human breast cell carcinogenesis in vitro
| Autor: | Daiane Cattani, Oskar Karlsson, Paula Pierozan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Carcinogenesis Health Toxicology and Mutagenesis Cell Breast Neoplasms Cell Cycle Proteins Genotoxicity and Carcinogenicity Toxicology medicine.disease_cause Cell Line Epigenesis Genetic Malignant transformation 03 medical and health sciences 0302 clinical medicine Breast cancer Cyclin D1 Cell Movement PFOS medicine Humans Epigenetics Cell Proliferation Fluorocarbons DNA methylation p21 biology Cell Cycle PFOA Correction Epithelial Cells General Medicine medicine.disease 030104 developmental biology medicine.anatomical_structure Alkanesulfonic Acids Cell transformation 030220 oncology & carcinogenesis Cancer research biology.protein Female Cyclin-dependent kinase 6 Caprylates Histone modification |
| Zdroj: | Archives of Toxicology Arch Toxicol |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | Gene–environment interactions are involved in the development of breast cancer, the tumor type that accounts for the majority of the cancer-related deaths among women. Here, we demonstrate that exposure to PFOS (10 µM) and PFOA (100 µM)—two contaminants ubiquitously found in human blood—for 72 h induced breast epithelial cell (MCF-10A cell line) proliferation and alteration of regulatory cell-cycle proteins (cyclin D1, CDK6, p21, p53, p27, ERK 1/2 and p38) that persisted after a multitude of cell divisions. The contaminants also promoted cell migration and invasion by reducing the levels of E-cadherin, occludin and β-integrin in the unexposed daughter cells. The compounds further induced an increase in global DNA methylation and differentially altered histone modifications, epigenetic mechanisms implicated in tumorigenesis. This mechanistic evidence for PFOS- and PFOA-induced malignant transformation of human breast cells supports a role of these abundant contaminants in the development and progression of breast cancer. Increased knowledge of contaminant-induced effects and their contribution to breast tumorigenesis is important for a better understanding of gene–environment interactions in the etiology of breast cancer. |
| Databáze: | OpenAIRE |
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