Genome stability of human embryonic stem cells (hESC) is an important issue because even minor genetic alterations can negatively impact cell functionality and safety. The incorrect repair of DNA double-stranded breaks (DSBs) is the ultimate cause of the formation of chromosomal aberrations. Using G2 radiosensitivity assay, we analyzed chromosomal aberrations in pluripotent stem cells and somatic cells. The chromatid exchange aberration rates in hESCs increased manifold 2 hours after irradiation as compared with their differentiated derivatives, but the frequency of radiation-induced chromatid breaks was similar. The rate of radiation-induced chromatid exchanges in hESCs and differentiated cells exhibited a quadratic dose response, revealing two-hit mechanism of exchange formation suggesting that a non-homologous end joining (NHEJ) repair may contribute to their formation. Inhibition of DNA-PK, a key NHEJ component, by NU7026 resulted in a significant decrease in radiation-induced chromatid exchanges in hESCs but not in somatic cells. In contrast, NU7026 treatment increased the frequency of radiation-induced breaks to a similar extent in pluripotent and somatic cells. Thus, DNA-PK dependent NHEJ efficiently participates in the elimination of radiation-induced chromatid breaks during the late G2 in both cell types and DNA-PK activity leads to a high level of misrejoining specifically in pluripotent cells.

Adenoid hypertrophy (AH) is considered one of the most common diseases in the ear, nose and throat (ENT) practice. The cause of adenoid hypertrophy in children is still unknown. The main aim of the current study was to investigate IL-10 (interleukin 10) gene polymorphisms and human herpesviruses 6 (HHV6), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) infections in children with AH. A total of 106 children with adenoid hypertrophy and 38 healthy children aged 2–11 years were included in this study. All children with adenoid hypertrophy were divided into three subgroups depending on the adenoid size. The viruses were determined via quantitative real-time polymerase chain reaction (PCR) using commercially available kits (QIAGEN, Germany). HHV6 was more frequently detected in patients with AH compared with CMV and EBV. Among the three subgroups of children with AH, HH6 and EBV were prevalent in the children with the largest adenoid size. The frequency of genotype GG tended to be higher in the control group of children. We found significantly higher frequencies of the G allele and GG and GA genotypes for IL-10 rs1800896 in the subgroup of children with the smallest size of adenoid compared with other subgroups. In conclusion, HHV6 and EBV infection could contribute to the adenoid size. The genotype GG for IL-10 rs1800896 could contribute to the resistance to adenoid hypertrophy and the spread of the adenoid tissue.

Introduction. Head and neck cancer is a heterogenous group of malignant tumors of different etiologies, molecular mechanisms of which are still insufficiently studied.Aim. Investigation of DNA methylation status of some tumor associated genes (RASSF1A, RASSF2, RASSF5, CDO1, MEST and WIF1) in patients with head and neck squamous cell carcinoma.Materials and methods. The DNA methylation level of normal and tumor tissues was analyzed using bisulfite conversion and methylation-sensitive high-resolution melting in 25 patients (21 men and 4 women) diagnosed with neck squamous cell carcinoma.Results. There were significant differences in levels of DNA methylation between tumor and normal tissues in the CDO1 and WIF1 genes in all groups and subgroups of patients (larynx and other cancers, squamous cell carcinoma keratinizing and non-keratinizing, primary and recurrent tumor, smokers and non-smokers). The methylation level in the CDO1 gene in tumor tissue was significantly increased in the T4 and T3 stage subgroups compared to T2.Conclusion. The increased level of methylation of the CDO1 and WIF1 genes, as well as changes in their expression are among the molecular mechanisms involved in the neck squamous cell carcinoma development. They can be considered as prognostic and diagnostic markers for this pathology.