Latest Publications

@article{brenerova_pure_2016,

title = {Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells.},

author = {Petra Brenerová and Timo Hamers and Jorke H. Kamstra and Jan Vondráček and Simona Strapáčová and Patrik L. Andersson and Miroslav Machala},

doi = {10.1007/s11356-015-4819-6},

issn = {1614-7499 0944-1344},

year  = {2016},

date = {2016-02-01},

journal = {Environmental science and pollution research international},

volume = {23},

number = {3},

pages = {2099–2107},

abstract = {The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 μM), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.},

note = {Place: Germany},

keywords = {Animals, Aryl hydrocarbon receptor, Aryl Hydrocarbon/genetics/*metabolism, Cell Line, Cell Proliferation/drug effects, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P450, Disruption of contact inhibition, DR-CALUX® assay, Epithelial Cells/cytology/drug effects/metabolism, Gene Expression/drug effects, Hepatocytes/cytology/drug effects/metabolism, Liver/*drug effects/metabolism, NDL-PCBs, Polychlorinated Biphenyls/*chemistry/*toxicity, Rats, Receptors, Relative effect potency, Signal Transduction/drug effects},

pubstate = {published},

tppubtype = {article}

}

@article{andrysik_aryl_2007,

title = {The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells.},

author = {Zdenek Andrysík and Jan Vondrácek and Miroslav Machala and Pavel Krcmár and Lenka Svihálková-Sindlerová and Anne Kranz and Carsten Weiss and Dagmar Faust and Alois Kozubík and Cornelia Dietrich},

doi = {10.1016/j.mrfmmm.2006.10.004},

issn = {0027-5107},

year  = {2007},

date = {2007-02-01},

journal = {Mutation research},

volume = {615},

number = {1-2},

pages = {87–97},

abstract = {Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their effects were significantly reduced in cells expressing a dominant-negative AhR mutant (dnAhR). Roscovitine, a chemical inhibitor of cdk2, abolished the induction of cell proliferation by BbF. However, neither BaA nor BbF modulated expression of the principal cdk inhibitor involved in maintenance of contact inhibition, p27(Kip1), or pRb phosphorylation. The strongly mutagenic BaP induced apoptosis, a decrease in total cell numbers and significantly higher percentage of cells entering S-phase than either BaA or BbF. Given that BaP induced high levels of Cyclin A/cdk2 activity, downregulation of p27(Kip1) and hyperphosphorylation of pRb, the accumulation of cells in S-phase was probably due to cell proliferation, although S-phase arrest due to blocked replication forks can not be excluded. Both types of effects of BaP were significantly attenuated in dnAhR cells. Transfection of WB-F344 cells with siRNA targeted against AhR decreased induction of Cyclin A induced by BbF or BaP, further supporting the role of AhR in proliferative effects of PAHs. This suggest that activation of AhR plays a significant role both in disruption of contact inhibition by weakly mutagenic PAHs and in genotoxic effects of BaP possibly leading to enhanced cell proliferation. Thus, PAHs may increase proliferative rate and the likelihood of fixation of mutations.},

note = {Place: Netherlands},

keywords = {Animals, Apoptosis/drug effects, Aryl Hydrocarbon/antagonists & inhibitors/genetics/*metabolism, Base Sequence, Benz(a)Anthracenes/toxicity, Benzo(a)pyrene/toxicity, Cell Cycle Proteins/metabolism, Cell Cycle/*drug effects/*physiology, Cell Line, Cell Proliferation/drug effects, Cyclin A/metabolism, Cyclin-Dependent Kinase 2/metabolism, Cytochrome P-450 CYP1A1/genetics, Epithelial Cells/cytology/drug effects/metabolism, Fluorenes/toxicity, Gene Expression/drug effects, Hepatocytes/cytology/*drug effects/*metabolism, Messenger/genetics/metabolism, Multiprotein Complexes, Mutagens/toxicity, Mutation, Polycyclic Aromatic Hydrocarbons/*toxicity, Rats, Receptors, RNA, Small Interfering/genetics},

pubstate = {published},

tppubtype = {article}

}