Affiliation:
1. Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
2. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France
Abstract
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.
Funder
European Union’s Horizon 2020
Spanish Ministry of Science and Innovation
Generalitat de Catalunya
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference137 articles.
1. (2022, December 05). Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology, Available online: https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCEA&dirEntryId=286690.
2. The 3Rs and animal welfare—Conflict or the way forward?;Rusche;Altern. Anim. Exp.,2003
3. Predicting human drug toxicity and safety via animal tests: Can any one species predict drug toxicity in any other, and do monkeys help?;Bailey;Altern. Lab. Anim.,2015
4. Lessons learned in applying the U.S. EPA proposed cancer guidelines to specific compounds;Andersen;Toxicol. Sci.,2000
5. A pragmatic approach for human risk assessment of chemical mixtures;Boberg;Curr. Opin. Toxicol.,2019
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