552bcc1a20d50cc56ea2fec43d11b172 In_Vitro_Approaches_to_Determine_the_Potential_Car.pdf 9d7e11432e4d45b92d221909964f344ef0b937c8 In_Vitro_Approaches_to_Determine_the_Potential_Car.pdf 21222dd32605a884e445bd21885fd732242921e73f2175fa915b0337d83beef3 In_Vitro_Approaches_to_Determine_the_Potential_Car.pdf Title: In Vitro Approaches to Determine the Potential Carcinogenic Risk of Environmental Pollutants Subject: One important environmental/health challenge is to determine, in a feasible way, the potential carcinogenic risk associated with environmental agents/exposures. Since a significant proportion of tumors have an environmental origin, detecting the potential carcinogenic risk of environmental agents is mandatory, as regulated by national and international agencies. The challenge mainly implies finding a way of how to overcome the inefficiencies of long-term trials with rodents when thousands of agents/exposures need to be tested. To such an end, the use of in vitro cell transformation assays (CTAs) was proposed, but the existing prevalidated CTAs do not cover the complexity associated with carcinogenesis processes and present serious limitations. To overcome such limitations, we propose to use a battery of assays covering most of the hallmarks of the carcinogenesis process. For the first time, we grouped such assays as early, intermediate, or advanced biomarkers which allow for the identification of the cells in the initiation, promotion or aggressive stages of tumorigenesis. Our proposal, as a novelty, points out that using a battery containing assays from all three groups can identify if a certain agent/exposure can pose a carcinogenic risk; furthermore, it can gather mechanistic insights into the mode of the action of a specific carcinogen. This structured battery could be very useful for any type of in vitro study, containing human cell lines aiming to detect the potential carcinogenic risks of environmental agents/exposures. In fact, here, we include examples in which these approaches were successfully applied. Finally, we provide a series of advantages that, we believe, contribute to the suitability of our proposed approach for the evaluation of exposure-induced carcinogenic effects and for the development of an alternative strategy for conducting an exposure risk assessment. Keywords: in vitro cell transformation; oncogenic phenotype; cancer hallmarks; long-term exposure Author: Irene Barguilla, Veronique Maguer-Satta, Boris Guyot, Susana Pastor, Ricard Marcos and Alba Hernández Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 26 16:11:27 2023 CEST ModDate: Wed Apr 26 16:17:31 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 26 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3754737 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GKYVXB+VnURWPalladioL Type 1 Custom yes yes no 10 0 YVKYZK+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 VAHASV+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 TGSQLW+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes 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368 0 FZLVCN+EURM7 Type 1 Builtin yes yes no 391 0 IOLAWT+PazoMath-Italic Type 1 Builtin yes yes no 417 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-13 02:39:37 CEST RepresentationInformation: In_Vitro_Approaches_to_Determine_the_Potential_Car.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-10 01:34:28 CEST Size: 3754737 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 849 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Long-Term Exposures as a Novel Approach for Carcinogenesis Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Alternative Cell Transformation Assays Based on the Hallmarks of Carcinogenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: In Vitro Cell Transformation Biomarkers and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Early Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Intermediate Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Advanced Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Representative Studies Using the Proposed Approach to Evaluate In Vitro Carcinogenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Conclusions and Further Steps Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Info: Title: In Vitro Approaches to Determine the Potential Carcinogenic Risk of Environmental Pollutants Author: Irene Barguilla, Veronique Maguer-Satta, Boris Guyot, Susana Pastor, Ricard Marcos and Alba Hernández Subject: One important environmental/health challenge is to determine, in a feasible way, the potential carcinogenic risk associated with environmental agents/exposures. Since a significant proportion of tumors have an environmental origin, detecting the potential carcinogenic risk of environmental agents is mandatory, as regulated by national and international agencies. The challenge mainly implies finding a way of how to overcome the inefficiencies of long-term trials with rodents when thousands of agents/exposures need to be tested. To such an end, the use of in vitro cell transformation assays (CTAs) was proposed, but the existing prevalidated CTAs do not cover the complexity associated with carcinogenesis processes and present serious limitations. To overcome such limitations, we propose to use a battery of assays covering most of the hallmarks of the carcinogenesis process. For the first time, we grouped such assays as early, intermediate, or advanced biomarkers which allow for the identification of the cells in the initiation, promotion or aggressive stages of tumorigenesis. Our proposal, as a novelty, points out that using a battery containing assays from all three groups can identify if a certain agent/exposure can pose a carcinogenic risk; furthermore, it can gather mechanistic insights into the mode of the action of a specific carcinogen. This structured battery could be very useful for any type of in vitro study, containing human cell lines aiming to detect the potential carcinogenic risks of environmental agents/exposures. In fact, here, we include examples in which these approaches were successfully applied. Finally, we provide a series of advantages that, we believe, contribute to the suitability of our proposed approach for the evaluation of exposure-induced carcinogenic effects and for the development of an alternative strategy for conducting an exposure risk assessment. 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