Modern alternative research methods in genetic toxicology (literature review)

Abstract

The review represents the current principles of assessment of chemicals genotoxicity. The main attention is paid to alternative research methods. The international experience of the application of alternative approaches and prospects of their use for regulatory purposes are discussed. The data for this review were collected from the Russian and foreign literature, as well as Internet resources, concerning the development of the new alternative methods for testing chemicals for genotoxicity. The OECD database, Scopus, Medline, Google Scholar, RISC, CyberLeninka were used for the information retrieval. Although the evaluation of genotoxicity of chemical substances is the well-established and based on the battery of validated methods, the studies for improving the existing tests and developing new technologies, including the alternative approaches, continue unabated up to now. In general, three trends of development of genetic toxicology can be outlined, including creating of new methods based on the whole-genome sequencing and the application of genome editing technologies; implementation of quantitative system of effects assessment in addition to the existing qualitative approach (mutagenic/non-mutagenic) and testing of various combinations of genotoxicity evaluation methods to identify a battery of tests with a greater predictive activity regarding carcinogenic effects. To use the developed alternative models for regulatory purposes, it is necessary to provide convincing evidence that the data obtained are good predictors of the organism’s actual response to the effects of toxicants/genotoxicants, validation of methods, standardization, and harmonization of research protocols, and changes to the existing regulatory framework are required.