In silico exploratory study using structure–activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay

P. Kamath, G. Raitano, A. Fernández, R. Rallo, E. Benfenati

Research output: Contribution to journalArticle

Abstract

The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure–activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity in vitro based on the Ames test and in vivo based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity in vitro, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity in vivo, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals in vitro and in vivo.

Original languageEnglish
Pages (from-to)1017-1031
Number of pages15
JournalSAR and QSAR in Environmental Research
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 2 2015

Keywords

  • in vitro
  • in vivo
  • metabolic pathway
  • REACH, mutagenicity
  • SAR

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Drug Discovery

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