7f8f2fe0894827d792720cf68b7065ca PH_003_22_As-PSNPLs_IntJMolSci.pdf 02b0cff456ddcf17a169ff6c436dd126e1a42a4a PH_003_22_As-PSNPLs_IntJMolSci.pdf 51710adc3e082c9f98dd3d3414c2d2cbf82a28f2138662b6f2f576a9f51f7413 PH_003_22_As-PSNPLs_IntJMolSci.pdf Title: Nanoplastics and Arsenic Co-Exposures Exacerbate Oncogenic Biomarkers under an In Vitro Long-Term Exposure Scenario Subject: The increasing accumulation of plastic waste and the widespread presence of its derivatives, micro- and nanoplastics (MNPLs), call for an urgent evaluation of their potential health risks. In the environment, MNPLs coexist with other known hazardous contaminants and, thus, an interesting question arises as to whether MNPLs can act as carriers of such pollutants, modulating their uptake and their harmful effects. In this context, we have examined the interaction and joint effects of two relevant water contaminants: arsenic and polystyrene nanoplastics (PSNPLs), the latter being a model of nanoplastics. Since both agents are persistent pollutants, their potential effects have been evaluated under a chronic exposure scenario and measuring different effect biomarkers involved in the cell transformation process. Mouse embryonic fibroblasts deficient for oxidative DNA damage repair mechanisms, and showing a cell transformation status, were used as a sensitive cell model. Such cells were exposed to PSNPLs, arsenic, and a combination PSNPLs/arsenic for 12 weeks. Interestingly, a physical interaction between both pollutants was demonstrated by using TEM/EDX methodologies. Results also indicate that the continuous co-exposure enhances the DNA damage and the aggressive features of the initially transformed phenotype. Remarkably, co-exposed cells present a higher proportion of spindle-like cells within the population, an increased capacity to grow independently of anchorage, as well as enhanced migrating and invading potential when compared to cells exposed to arsenic or PSNPLs alone. This study highlights the need for further studies exploring the long-term effects of contaminants of emerging concern, such as MNPLs, and the importance of considering the behavior of mixtures as part of the hazard and human risk assessment approaches. Keywords: polystyrene nanoplastics; arsenic; long-term co-exposure; cell transformation; DNA damage; oncogenic phenotype; carcinogenesis Author: Irene Barguilla, Josefa Domenech, Laura Rubio, Ricard Marcos and Alba Hernández Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 10 08:48:44 2022 CET ModDate: Thu Mar 10 09:36:44 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3645233 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AWHDWW+VnURWPalladioL Type 1 Custom yes yes no 10 0 MLVPVC+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 RNEVUZ+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 CDCXMQ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular 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Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: PSNPLs and y-PSNPLs Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Cell Culture Conditions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: PSNPLs Uptake by PTP Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: PSNPLs/AsIII Interaction Detection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: AsIII Internalization by PTP Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: In Vitro Chronic PSNPLs and Arsenic (Co)Exposure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Comet Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Cell Morphology and Spindle-like-Cell Proportion Calculation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Anchorage-Independent Growth Induction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Invasion and Migration Induction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Tumorsphere Formation Induction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: PS Materials Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Determination and Quantification of y-PSNPLs Uptake by PTP Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Visualization of the PSNPLs/AsIII Interaction in Dispersion, and Quantification of AsIII Uptake by PTP Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Both the Co-Exposure and the Single Pollutants Exposure Induce DNA Damage Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: The PTP Oncogenic Phenotype Is Exacerbated by the Long-Term Co-Exposure to AsIII and PSNPLs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: The Increased Aggressiveness of PTC’s Oncogenic Phenotype Is Not Related to an Increasing Stem-like Cells Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Discussions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Nanoplastics and Arsenic Co-Exposures Exacerbate Oncogenic Biomarkers under an In Vitro Long-Term Exposure Scenario Author: Irene Barguilla, Josefa Domenech, Laura Rubio, Ricard Marcos and Alba Hernández Subject: The increasing accumulation of plastic waste and the widespread presence of its derivatives, micro- and nanoplastics (MNPLs), call for an urgent evaluation of their potential health risks. In the environment, MNPLs coexist with other known hazardous contaminants and, thus, an interesting question arises as to whether MNPLs can act as carriers of such pollutants, modulating their uptake and their harmful effects. In this context, we have examined the interaction and joint effects of two relevant water contaminants: arsenic and polystyrene nanoplastics (PSNPLs), the latter being a model of nanoplastics. Since both agents are persistent pollutants, their potential effects have been evaluated under a chronic exposure scenario and measuring different effect biomarkers involved in the cell transformation process. Mouse embryonic fibroblasts deficient for oxidative DNA damage repair mechanisms, and showing a cell transformation status, were used as a sensitive cell model. Such cells were exposed to PSNPLs, arsenic, and a combination PSNPLs/arsenic for 12 weeks. Interestingly, a physical interaction between both pollutants was demonstrated by using TEM/EDX methodologies. Results also indicate that the continuous co-exposure enhances the DNA damage and the aggressive features of the initially transformed phenotype. Remarkably, co-exposed cells present a higher proportion of spindle-like cells within the population, an increased capacity to grow independently of anchorage, as well as enhanced migrating and invading potential when compared to cells exposed to arsenic or PSNPLs alone. This study highlights the need for further studies exploring the long-term effects of contaminants of emerging concern, such as MNPLs, and the importance of considering the behavior of mixtures as part of the hazard and human risk assessment approaches. 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