Toxic Effects of Methylated Benzo[a]pyrenes in Rat Liver Stem-Like Cells

0365862 - ÚEM 2012 RIV US eng J - Journal Article
Trilecová, L. - Krčková, S. - Marvanová, S. - Pěnčíková, K. - Krčmář, P. - Neča, J. - Hulínková, P. - Pálková, L. - Ciganek, M. - Milcová, Alena - Topinka, Jan - Vondráček, Jan - Machala, M.
Toxic Effects of Methylated Benzo[a]pyrenes in Rat Liver Stem-Like Cells.
Chemical Research in Toxicology. Roč. 24, č. 6 (2011), s. 866-876. ISSN 0893-228X. E-ISSN 1520-5010
Grant - others:GA ČR(CZ) GA525/08/1590
Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50040702
Keywords : Ah receptor * DNA adducts * WB F344 cells
Subject RIV: DN - Health Impact of the Environment Quality
Impact factor: 3.779, year: 2011

AhR-mediated activity of five selected MeBaP isomers was estimated in the DR-CALUX reporter gene assay performed in rat hepatoma 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. Importantly, 1-MeBaP and 3-MeBaP were found to be potent AhR agonists, 1 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.
Permanent Link: http://hdl.handle.net/11104/0201007