Telomerase gene expression bioassays indicate metabolic activation of genotoxic lower chlorinated polychlorinated biphenyls

作者: Theresa Vasko , Jenny Hoffmann , Sonja Gostek , Thomas Schettgen , Natalia Quinete

DOI: 10.1038/S41598-018-35043-W

关键词: Mitochondrial respiratory chainMTT assayMolecular biologyBioassayRegulation of gene expressionChemistryDNA damageGene expressionLowest-observed-adverse-effect levelToxicity

摘要: Polychlorinated biphenyls (PCBs) are ubiquitously occurring pollutants with different chemical and toxicological properties. In this study we evaluated blood plasma samples of two PCB-exposed cohorts for their ability to alter telomerase (hTERT) gene expression. Blood from individuals inhibited hTERT expression depending solely on the concentration lower chlorinated PCBs, lowest observed adverse effect level (LOAEL) at a between 0.5 2 µg/L LC PCBs. Individual OH-metabolites derived WHO indicator congeners PCB 28 101 mimicked these effects in vitro high toxicity, including DNA damage. However, by combination OH-metabolites, bio effective was reduced respective could be increased. At which showed no toxic activity MTT assay, inhibition reflected interference OH-PCBs mitochondrial respiratory chain, lead production reactive oxygen species (ROS). As individual already much stronger than parental compounds, bioassay described seems indicate metabolic activation PCBs rather mere own. summary, provides dose-response linkages concentrations human plasma.

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