Abstract Investigation of A. thaliana accessions from the Chornobyl zone revealed their increased tolerance to cadmium (Cd2+) and radiomimetics (bleomycin/zeocin). Thus, seedlings of the Chornobyl accession Che07 demonstrated reduced inhibition of root growth under Cd-induced stress. It was observed for the first time that zeocin mainly affects the cells of the root meristem, whereas Cd2+ predominantly affects cells of the elongation zone. This differential response may be due to variations in the stages of cell development, the specificity of genotoxic agents, and the activity of defense mechanisms in different growth zones of the root. Analysis of DNA damage and repair capacity revealed a rapid (within 3 min) activation of repair mechanisms in the Chornobyl A. thaliana accessions Che5 and Che07 after treatment with radiomimetic. Increased expression of the cyclin gene CycB2;1 and decreased expression of the CDKG1 kinase gene after treatment with bleomycin indicate changes in the regulation of the cell cycle, specifically an arrest at the G2 phase. Such an adaptive response likely functions to suppress mitotic entry, which prevents the transfer of damaged DNA to daughter cells. In A. thaliana accessions from the Chornobyl zone, the activation of specific antioxidant enzymes was observed, which counteracts oxidative stress and damage to the genome. It is assumed that A. thaliana from the Chornobyl zone develop unique mechanisms of adaptation to environmental stress and DNA damage, caused by ionizing agents. Investigating the tolerance of plants to ionizing radiation and heavy metals is important for the development of phytoremediation strategies as well as biotechnologies to improve resistance to other abiotic stress factors.