Expression of the CDKN1A, MDM2, and ATM genes as a biomarker of the toxic effect of heavy metals (literature review)

The development of new approaches enabling differentiation of a wide range of toxic effects can significantly improve risk assessment. To understand the response mechanisms at the molecular level, it is important to study the expression of genes responsible for DNA repair, since this process is one of the early responses to toxic effects. The purpose of the study was to summarize available data on the expression of repair CDKN1A, MDM2, and ATM genes associated with toxic effects of exposure to heavy metals. A systematic search was carried out to identify studies on a given topic in the PubMed, Web of Science, eLIBRARY and Google Scholar electronic databases using the following keywords: heavy metals, CDKN1A, MDM2, ATM, toxicity, DNA repair, and gene expression. The initial search for scientific publications was carried out independently by three authors; then all sources found were checked and compared to filter out duplicate papers. This review covers 50 literature sources. The analysis of toxicogenome studies allowed us to identify several genes for assessing heavy metal toxicity among a large number of candidate biomarkers. The most commonly considered genes are the p21/CDKN1A gene, the MDM2 proto-oncogene, and the ATM gene. Limitations. The review is limited to considering changes in the expression of only a small number of genes responsible for DNA repair. Conclusion. The expression of the above biomarker genes provides a detailed picture of the response of a biological system to hazardous exposures and can be used as part of the assessment of toxic effects.