Genotoxicity testing: progress and prospects for the next decade

Expert Opin Drug Metab Toxicol. 2017 Oct;13(10):1089-1098. doi: 10.1080/17425255.2017.1375097. Epub 2017 Sep 10.

Abstract

Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages. The limitations that have arisen as a result of the common use of these methods were also discussed. Finally, the perspectives of further prospects on the use of genotoxicity testing and genotoxic mode of action were emphasized. Expert opinion: The solution of actual and practical problems of genetic toxicology is inarguably based on the understanding of DNA damage mechanisms at molecular, subcellular, cellular, organ, system and organism levels. Current strategies to investigate human health risks should be modified to increase their performance for more reliable results and also new techniques such as toxicogenomics, epigenomics and single cell approaches must be integrated into genetic safety evolutions. The explored new biomarkers by the omic techniques will provide forceful genotoxicity assessment to reduce the cancer risk.

Keywords: Genetic toxicity; genotoxicity testing strategies; omics; risk assessment; short term assays.

Publication types

  • Review

MeSH terms

  • Agrochemicals / toxicity
  • Animals
  • Cosmetics / toxicity
  • DNA Damage / drug effects
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Epigenomics / methods
  • Food Additives / toxicity
  • Humans
  • Mutagenicity Tests / methods*
  • Mutagenicity Tests / trends
  • Mutagens / toxicity*
  • Point Mutation
  • Risk Assessment / methods*
  • Toxicogenetics / methods

Substances

  • Agrochemicals
  • Cosmetics
  • Food Additives
  • Mutagens