Abstract
Due to the link with serious adverse health effects, genotoxicity is an important toxicological endpoint in each regulatory setting with respect to human health, including for pharmaceuticals. To this extent, a compound potential to induce gene mutations as well as chromosome damage needs to be addressed. For chromosome damage, i.e., the induction of structural or numerical chromosome aberrations, several in vitro and in vivo test methods are available. In order to rapidly collect toxicological data without the need for test material, several in silico tools for chromosome damage have been developed over the last years. In this chapter, a battery of freely available in silico chromosome damage prediction tools for chromosome damage is applied on a dataset of pharmaceuticals. Examples of the different outcomes obtained with the in silico battery are provided and briefly discussed. Furthermore, results for coumarin are presented in more detail as a case study. Overall, it can be concluded that although they are in general less developed than those for mutagenicity, in silico tools for chromosome damage can provide valuable information, especially when combined in a battery.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Griffiths AJF, Wessler SR, Lewontin RC, Gelbart WM, Suzuki DT, Miller JH (2005) Introduction to genetic analysis, 8th edn. Holtzbrinck, Stuttgart, Germany, p 850
Basu AK (2018) DNA damage, mutagenesis and cancer. Int J Mol Sci 19:970
ECVAM (2013) EURL ECVAM strategy to avoid and reduce animal use in genotoxicity testing. In: JRC Scientific and Policy Report. https://doi.org/10.2788/43865
European Food Safety Authority (EFSA) (2011) Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA J 9(9):2379
ICH (2013) ICH guideline S2 (R1) on genotoxicity testing and data interpretation for pharmaceuticals intended for human use. Available at https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-s2-r1-genotoxicity-testing-data-interpretation-pharmaceuticals-intended-human-use-step_en.pdf
Organisation for Economic Co-Operation and Development (2017) Overview on genetic toxicology TGs, OECD series on testing and assessment, no. 238. OECD Publishing, Paris, France, p 60. https://doi.org/10.1787/9789264274761-en
Van Bossuyt M, Raitano G, Honma M, Van Hoeck E, Vanhaecke T, Rogiers V, Mertens B, Benfenati E (2020) New QSAR models to predict chromosome damaging potential based on the in vivo micronucleus test. Toxicol Lett 329:80–84
Benigni R, Serafimova R, Parra Morte JM, Battistelli CL, Bossa C, Giuliani A, Fioravanzo E, Bassan A, Gatnik MF, Rathman J, Yang C, Mostrag-Szlichtyng A, Sacher O, Tcheremenskaia O (2020) Evaluation of the applicability of existing (Q)SAR models for predicting the genotoxicity of pesticides and similarity analysis related with genotoxicity of pesticides for facilitating of grouping and read across: an EFSA funded project. Regul Toxicol Pharmacol 114:104658
Benigni R, Bossa C, Tcheremenskaia O, Battistelli CL, Crettaz P (2012) The new ISSMIC database on in vivo micronucleus and its role in assessing genotoxicity testing strategies. Mutagenesis 27:87–92. https://doi.org/10.1093/mutage/ger064
Lea IA, Gong H, Paleja A, Rashid A, Fostel J (2017) CEBS: a comprehensive annotated database of toxicological data. Nucleic Acids Res 45:D964–D971. https://doi.org/10.1093/nar/gkw1077
Danish (Q)SAR Database, Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, http://qsar.food.dtu.dk
Baderna D, Gadaleta D, Lostaglio E, Selvestrel G, Raitano G, Golbamaki A, Lombardo A, Benfenati E (2020) New in silico models to predict in vitro micronucleus induction as marker of genotoxicity. J Hazard Mater 385:121638
Toropov AA, Toropova AP, Raitano G, Benfenati E (2019) CORAL: building up QSAR models for the chromosome aberration test. Saudi J Biol Sci 26:1101–1106
Benigni R, Bossa C, Worth A (2010) Structural analysis and predictive value of the rodent in vivo micronucleus assay results. Mutagenesis 25(4):335–341
Garg SS, Gupta J, Sharma S, Sahu D (2020) An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur J Pharm Sci 152:105424
Acknowledgments
The research for this paper was financially supported by the LIFE VERMEER project (LIFE16 ENV/IT/OOO167).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Baderna, D., Van Overmeire, I., Lavado, G.J., Gadaleta, D., Mertens, B. (2022). In Silico Methods for Chromosome Damage. In: Benfenati, E. (eds) In Silico Methods for Predicting Drug Toxicity. Methods in Molecular Biology, vol 2425. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1960-5_8
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1960-5_8
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1959-9
Online ISBN: 978-1-0716-1960-5
eBook Packages: Springer Protocols