Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.

• Klíčová slova
• 8OHdG, DNA strand break damage, arterial hypertension, cardiovascular disease, comet assay, gammaH2AX,
• MeSH
• 8-hydroxy-2'-deoxyguanosin MeSH
• biologické markery krev   MeSH
• hypertenze * MeSH
• kometový test MeSH
• lidé MeSH
• oxidační stres MeSH
• poškození DNA * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• 8-hydroxy-2'-deoxyguanosin MeSH
• biologické markery MeSH

Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase. We rescued infertility in male hybrids with bacterial artificial chromosomes carrying Prdm9 from a strain with the "fertility" Hst1(f) allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize gammaH2AX into the pachynema sex (XY) body. These defects, seen also in Prdm9-null mutants, are rescued by the Prdm9 transgene. Identification of a vertebrate hybrid sterility gene reveals a role for epigenetics in speciation and opens a window to a hybrid sterility gene network.

• MeSH
• epigeneze genetická MeSH
• histonlysin-N-methyltransferasa chemie   genetika   metabolismus   MeSH
• histony metabolismus   MeSH
• hybridizace genetická MeSH
• křížení genetické MeSH
• mapování chromozomů MeSH
• meióza * MeSH
• metylace MeSH
• molekulární sekvence - údaje MeSH
• mužská infertilita genetika   MeSH
• myši inbrední C3H MeSH
• myši transgenní MeSH
• myši MeSH
• ovarium enzymologie   MeSH
• regulace genové exprese MeSH
• sekvence aminokyselin MeSH
• testis enzymologie   MeSH
• umělé bakteriální chromozomy MeSH
• vznik druhů (genetika) * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• histony MeSH
• prdm9 protein, mouse MeSH Prohlížeč

Autosomal trisomies and monosomies bring serious threats to embryonic development through transcriptional disarray caused primarily by the dosage effect of the aneuploid part of the genome. The present study compared the effect of a mouse-viable 30-Mb segmental trisomy on the genome-wide transcriptional profile of somatic (liver) cells and male germ cells. Although the 1.6-fold change in expression of triplicated genes reflected the gene dosage in liver cells, the extra copy genes were compensated in early pachytene spermatocytes, showing 1.18-fold increase. Although more pronounced, the dosage compensation of trisomic genes was concordant with the incidence of HORMAD2 protein and histone gammaH2AX markers of unsynapsed chromatin. A possible explanation for this includes insufficient sensitivity to detect the meiotic silencing of unsynapsed chromatin markers in the 30-Mb region of the chromosome or an earlier silencing effect of another epigenetic factor. Taken together, our results indicate that the meiotic silencing of unsynapsed chromatin is the major, but most likely not the only, factor driving the dosage compensation of triplicated genes in primary spermatocytes.

• Klíčová slova
• gene dosage, male sterility, meiotic silencing of unsynapsed chromatin, pachytene spermatocytes, segmental trisomy, synaptonemal complex, transcriptional profiling,
• MeSH
• aneuploidie MeSH
• chromatin genetika   MeSH
• fenotyp MeSH
• genom * MeSH
• játra fyziologie   MeSH
• kompenzace dávky (genetika) * MeSH
• meióza genetika   MeSH
• mužská infertilita genetika   MeSH
• myši inbrední C57BL MeSH
• spermatocyty fyziologie   MeSH
• synaptonemální komplex genetika   MeSH
• těhotenství MeSH
• tělesná hmotnost genetika   MeSH
• transkriptom MeSH
• translokace genetická genetika   MeSH
• trizomie genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin MeSH

Cytolethal distending toxins (CDTs) are proteins produced and secreted by facultative pathogenic strains of Gram-negative bacteria with potentially genotoxic effects. Mammalian cells exposed to CDTs undergo cell type-dependent cell-cycle arrest or apoptosis; however, the cell fate responses to such intoxication are mechanistically incompletely understood. Here we show that both normal and cancer cells (BJ, IMR-90 and WI-38 fibroblasts, HeLa and U2-OS cell lines) that survive the acute phase of intoxication by Haemophilus ducreyi CDT possess the hallmarks of cellular senescence. This characteristic phenotype included persistently activated DNA damage signalling (detected as 53BP1/gammaH2AX(+) foci), enhanced senescence-associated beta-galactosidase activity, expansion of promyelocytic leukaemia nuclear compartments and induced expression of several cytokines (especially interleukins IL-6, IL-8 and IL-24), overall features shared by cells undergoing replicative or premature cellular senescence. We conclude that analogous to oncogenic, oxidative and replicative stresses, bacterial intoxication represents another pathophysiological stimulus that induces premature senescence, an intrinsic cellular response that may mechanistically underlie the 'distended' morphology evoked by CDTs. Finally, the activation of the two anticancer barriers, apoptosis and cellular senescence, together with evidence of chromosomal aberrations (micronucleation) reported here, support the emerging genotoxic and potentially oncogenic effects of this group of bacterial toxins, and warrant further investigation of their role(s) in human disease.

• MeSH
• bakteriální toxiny metabolismus   farmakologie   MeSH
• buněčný cyklus účinky léků   MeSH
• cyklin-dependentní kinasy antagonisté a inhibitory   metabolismus   MeSH
• cytokiny metabolismus   MeSH
• fenotyp MeSH
• Haemophilus ducreyi metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie * účinky léků   fyziologie   MeSH
• poškození DNA * MeSH
• signální transdukce fyziologie   MeSH
• stárnutí buněk fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální toxiny MeSH
• cyklin-dependentní kinasy MeSH
• cytokiny MeSH
• cytolethal distending toxin MeSH Prohlížeč

Bohemine and roscovitine are the most important representatives of the group of compounds structurally derived from olomoucine. Biologically they function as inhibitors of cyclin-dependent kinases (CDKs), the key regulators of cell cycle, which is often disrupted in cancer cells resulting in uncontrollable proliferation. Bohemine and roscovitine have demonstrated their cytostatic and cytotoxic in vitro and also in vivo effects. Currently the phase II clinical trials for roscovitine are underway. The aim of the study was to evaluate the potential in vitro radiosensitising effect of bohemine (BOH) and roscovitine (ROS). Clonogenic survival assay and human lung adenocarcinoma cell line A549 were used. Tested schedules were: A-pretreatment, B-concomitant application and C-posttreatment. Concentrations corresponded to IC10, IC25 and IC50 for BOH/ROS (0.1-30 microM). The radiation doses were 1, 2 and 3 Gy. Flow cytometry and western blot analysis were used to characterize cell cycle distribution, BrdU incorporation and DNA repair processes. The highest in vitro radiosensitising effect of BOH/ROS was observed for Schedule A in all tested concentrations (SER(37%) 1.46-3.20). Cell cycle analysis showed an inclination towards G0/G1 delay 48 hours posttreatment and unaltered level of apoptosis. Changes in the DNA repair processes were observed - inhibition of DNA-PK kinase, inhibition of BrdU incorporation, strong and enduring induction of p21 protein and long-lasting phosphorylation of gammaH2AX(Ser139). Certain low concentration activities of BOH/ROS in monotherapy were detected, mainly the activation of DNA-PK kinase. The results demonstrated strong in vitro radiosensitising effect of BOH/ROS that is concentration and especially schedule dependent. The strong cytostatic effect of the pretreatment schedule is mediated through the inhibition/rearrangements of DNA repair processes.

• MeSH
• adenokarcinom farmakoterapie   patologie   radioterapie   MeSH
• apoptóza účinky léků   účinky záření   MeSH
• buněčný cyklus účinky léků   účinky záření   MeSH
• cyklin-dependentní kinasy antagonisté a inhibitory   metabolismus   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kinetin farmakologie   MeSH
• lidé MeSH
• nádorové buňky kultivované účinky léků   MeSH
• nádory plic farmakoterapie   radioterapie   MeSH
• průtoková cytometrie MeSH
• puriny farmakologie   MeSH
• radiosenzibilizující látky farmakologie   MeSH
• rentgenové záření MeSH
• roskovitin MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bohemine MeSH Prohlížeč
• cyklin-dependentní kinasy MeSH
• inhibitory proteinkinas MeSH
• kinetin MeSH
• olomoucine MeSH Prohlížeč
• puriny MeSH
• radiosenzibilizující látky MeSH
• roskovitin MeSH