T regulační lymfocyty patří do skupiny T lymfocytů, které tlumí imunitní funkce organismu. Hrají důležitou roli v imunitní toleranci plodu v těhotenství, během kterého dochází ke změně jejich počtu v periferní krvi. Existuje již několik studií, které se zabývaly hladinou T regulačních lymfocytů v jednotlivých trimestrech těhotenství, ne však vždy se stejným výsledkem. Cílem této studie bylo zjistit procentuální zastoupení T regulačních lymfocytů během jednotlivých trimestrů, porovnat výsledky s některými již proběhlými studiemi a zjistit, zda má hladina T re-gulačních lymfocytů souvislost s preeklampsií, hypertenzí anebo potratem.
T regulatory lymphocytes belong to group of T-lymphocytes which inhibit immune function of organism. T regulatory lymphocytes play im-portant role in immune tolerance of the fetus during pregnancy, during which their number in peripheral blood is changing. Studies on level of T regulatory lymphocytes in several trimesters of pregnancy exist, however the results differ. The goal of this study was to define percentual representation of T regulatory lymphocytes during each trimester, compare results with some existing studies and define whether level of T re-gulatory lymphocytes has impact on pre-eclampsia, hypertension or abortion.
The methylated benzo[a]pyrenes (MeBaPs) are present at significant levels in the environment, especially in the sediments contaminated by petrogenic PAHs. However, the existing data on their toxic effects in vitro and/or in vivo are still largely incomplete. Transcription factor AhR plays a key role in the metabolic activation of PAHs to genotoxic metabolites, but the AhR activation may also contribute to the tumor promoting effects of PAHs. In this study, the AhR-mediated activity of five selected MeBaP isomers was estimated in the DR-CALUX reporter gene assay performed in rat hepatoma cells. Detection of other effects, including induction of CYP1A1, CYP1B1, and AKR1C9 mRNAs, DNA adduct formation, production of reactive oxygen species, oxidation of deoxyguanosine, and cell cycle modulation and apoptosis, was performed in the rat liver epithelial WB-F344 cell line, a model of liver progenitor cells. We identified 1-MeBaP as the most potent inducer of AhR activation, stable DNA adduct formation, checkpoint kinase 1 and p53 phosphorylation, and apoptosis. These effects suggest that 1-MeBaP is a potent genotoxin eliciting a typical sequence of events ascribed to carcinogenic PAHs: induction of CYP1 enzymes, formation of high levels of DNA adducts, activation of DNA damage responses (including p53 phosphorylation), and cell death. In contrast, 10-MeBaP, representing BaP isomers substituted with the methyl group in the angular ring, elicited only low levels DNA adduct formation and apoptosis. Other MeBaPs under study also elicited strong apoptotic responses associated with DNA adduct formation as the prevalent mode of toxic action of these compounds in liver cells. MeBaPs induced a weak production of ROS, which did not lead to significant oxidative DNA damage. Importantly, 1-MeBaP and 3-MeBaP were found to be potent AhR agonists, one order of magnitude more potent than BaP, thus suggesting that the AhR-dependent modulations of gene expression, deregulation of cell survival mechanisms, and further nongenotoxic effects associated with AhR activation may further contribute to their tumor promotion and carcinogenicity.
- MeSH
- DNA Adducts metabolism MeSH
- Apoptosis drug effects MeSH
- Benzo(a)pyrene chemistry toxicity MeSH
- Cell Line MeSH
- Cell Cycle drug effects MeSH
- Epithelial Cells drug effects metabolism MeSH
- Liver cytology MeSH
- Stem Cells drug effects metabolism MeSH
- Rats MeSH
- Methylation MeSH
- Mutagens chemistry toxicity MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Oxidative Stress drug effects MeSH
- Protein Kinases metabolism MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
