Histone deacetylase inhibitors (HDACi) suppress the growth of tumor cells due to the induction of cell cycle arrest, senescence or apoptosis (1-2). There are a few data concerning the reduction of DNA repair capability by HDACi in tumor cells (3-4). Previously we established that HDACi-induced G1/S cell cycle arrest of E1A+Ras-transformed mouse embryonic fibroblasts was accompanied with an accumulation of the marker of damaged DNA - γH2AX foci (5). Among all DNA damages, the double-strand breaks (DSB) are the most crucial for a cell. Since non-homologous end joining (NHEJ) is a principal repair mechanism of DSB whatever of the cell cycle phase, we focused our research on this repair mechanism. The aim of this study is to compare the DNA repair efficiency in transformed and normal cells after HDACi treatment. Methods: To model the NHEJ repair mechanism we used the host-cell reactivation assay. A luciferase reporter vector pGL3-luc was damaged with endonuclease and etoposide, and then introduced into E1A+Ras-transformed and normal (NIH3T3) mouse fibroblasts, using lipofectamine transfection. Transfected cells were incubated in the presence or absence of HDACi sodium butyrate and afterwards, the efficiency of DNA repair was evaluated by measurement of the luciferase activity. Results: Double-strand breaks, which were introduced by a damaging agent or an endonuclease into the plasmid DNA, decreased luciferase transcription. However, it reclaimed afterwards owing to DNA repair. We have shown that the recovery of DNA has occurred less efficiently in the presence of sodium butyrate in transformed cells, while in normal fibroblasts sodium butyrate did not affect the NHEJ-repair efficiency. Further, the HDACi suppressed the expression of repair proteins (Ku80, Ku70, Mre11) in transformed, but not in normal cells. Conclusions: We have thus demonstrated a fundamental difference between the influence of HDACi on DNA repair via NHEJ-mechanism in oncogene-transformed and in normal cells. DNA repair capability of E1A+Ras-transformed cells was reduced by HDACi, but in normal cells it stays unaffected. This effect is very useful for anticancer chemotherapy since HDACi could be applied in combination with DNA damage agents. Acknowledgments: A project is financed by RSF 19-75-10060. References: 1. Wang Y. et al., Cancer Lett. 2017; 400: 47-60; 2. Sun G. et al., Journal of cancer 2015; 6(10): 996-1004; 3. Rossiello F. et al., Curr Opin Genet Dev. 2014;26: 89-95; 4. Munshi, A. et al. Clin. Cancer Res. 2005; 11: 4912–22; 5. Abramova, M. V. et al. Cancer Biol Ther. 2011; 12(12): 1069-77.