Genome instability in peripheral blood lymphocytes of patients with heart failure and reduced ejection fraction.

Heart failure (HF) is a complex clinical condition characterized by functional and structural defects of the myocardium, but genetic and environmental factors are considered to play an important role in the development of the disease. In the present study, we investigated the genome instability (DNA and chromosomal damage) in patients with heart failure with reduced ejection fraction (HFrEF) ≤40% and its association with risk factors. The studied population included 48 individuals, of which 29 HFrEF patients (mean age 57.41 ± 5.74 years) and 19 healthy controls (mean age 57.63 ± 6.09 years). The genetic damage index in peripheral blood lymphocytes was analyzed using the comet assay, while micronuclei frequency and nuclear division index were analyzed using the cytokinesis-block micronucleus assay. Our results showed that HFrEF patients had a significantly higher genetic damage index compared with the healthy controls (P < .001). Cytokinesis-block micronucleus assay showed that the average micronucleus frequency in peripheral blood lymphocytes of patients was significantly higher, while the nuclear division index values were significantly lower than in controls (P < .01). Using multiple linear regression analysis, pathological state, ejection fraction, creatinine, glucose, associated disease, residence, proBNP, troponin, urea, ACE-inhibitors, and length of the drug therapy were identified as predictors of DNA and/or chromosomal damage in HF patients. We can conclude that DNA and chromosomal damage was increased in patients with HF, which may be a consequence of disease and/or drug therapy.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

Methanol extracts of Teucrium arduini L. and Teucrium flavum L. induce protective effect against mitomycin C in human lymphocytes in vitro.

The study was designed to evaluate antigenotoxic effect of methanol Teucrium arduini and Teucrium flavum extracts against mitomycin C (MMC)-induced chromosome and DNA damage in vitro. Cytokinesis-block micronucleus (CBMN) and comet assays were used to investigate effect of plant extracts in different concentrations (125, 250, 500 and 1000 µg/mL) on human peripheral blood lymphocytes (PBLs). The obtained results showed that the all tested concentrations of T. arduini and the highest concentration of T. flavum significantly reduced the MMC-induced micronucleus (MN) frequency in comparison to positive control (only MMC). There were significantly negative correlations between the extracts concentrations and MN frequencies (Pearson, r = -0.905, p = 0.0001 for T. arduini; r = -0.861, p = 0.0001 for T. flavum). The extracts of both plants further lowered the MMC-decreased nuclear division index (NDI) in a dose dependent-manner (Pearson, r = -0.837, p = 0.001 for T. arduini; r = -0.598, p = 0.040 for T. flavum), but significantly only in the highest concentration (1000 µg/mL). Comet assay showed that extracts reduced MMC-increased genetic damage index (GDI), significantly in the concentrations of 500 and 1000 µg/mL, in comparison with positive control. Based on our results, it can be concluded that methanol T. arduini and T. flavum extracts possess protective proapoptotic and antigenotoxic effect which is indication of their medicinal relevance and use in treatment.

Assessment of Chromosomal Damage in Umbilical Blood Lymphocytes of Newborns from Kragujevac in Central Serbia Born 18 Years after Environmental Contamination.

The measurement of micronuclei (MN) in umbilical blood lymphocytes of newborns are increasingly used in cytogenetic epidemiology as one of the preferred methods for assessing chromosomal damage resulted from maternal exposure to mutagen. In the present study, we evaluated the effect of strong environmental contamination (EC) (which occured in the City of Kragujevac, Central Serbia in 1999) on the MN frequency in group of 22 newborns born in Kragujevac 18 years after EC, using cytokinesis-block micronucleus (CBMN) assay. The mean MN frequency in umbilical lymphocytes of these newborns was 5.14 ± 2.17/1,000 binucleated (BN) cells, which is significantly lower than mean MN frequency of newborns born 12 months after contamination (9.36 ± 5.60/1,000 BN cells). Sex of newborns, age of mothers, cigarette smoking, and number of pregnancies did not affect the MN frequency of newborns. Our results showed that in utero exposure to environmental pollution affected genome instability of the fetuses, but that by improving the quality of environmental conditions there was a decrease in mean MN frequency of newborns born 18 years after contamination. In general, genome of umbilical lymphocytes shows a realistic picture of all changes in body and the environment.