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Published on: March 31, 2022
In Silico Methods for Chromosome Damage
Diego Baderna1, Ilse Van Overmeire2, Giovanna J Lavado1
1Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Lombardia, Italy.
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.
Insights
In silico tools can predict chromosome damage in pharmaceuticals, aiding regulatory toxicology. A battery of these computational methods offers valuable insights, especially when used together.
Area of Science:
- Toxicology
- Computational chemistry
- Pharmacology
Background:
- Genotoxicity is critical for human health assessment in pharmaceutical regulation.
- Assessing a compound's potential for gene mutations and chromosome damage is essential.
- Traditional in vitro and in vivo methods for chromosome damage assessment exist.
Purpose of the Study:
- To evaluate freely available in silico tools for predicting chromosome damage.
- To apply a battery of these computational tools to a pharmaceutical dataset.
- To analyze the utility of in silico approaches for genotoxicity testing.
Main Methods:
- A collection of freely accessible in silico chromosome damage prediction tools was utilized.
- These tools were applied to a dataset comprising various pharmaceuticals.
- The outcomes from the in silico battery were analyzed and discussed, including a case study on coumarin.
Main Results:
- In silico tools for chromosome damage prediction were applied to pharmaceutical compounds.
- Examples of diverse outcomes from the computational battery were presented.
- A detailed case study using coumarin illustrated the application and results of the in silico approach.
Conclusions:
- In silico tools for chromosome damage, while less developed than mutagenicity predictors, offer significant value.
- Combining multiple in silico tools in a battery enhances their predictive power.
- These computational methods provide valuable toxicological data for pharmaceuticals, especially in early assessments.
