Other formats:
BibTeX
LaTeX
RIS
@article{1138900, author = {Šmerdová, Lenka and Neča, Jiří and Svobodová, Jana and Topinka, Jan and Schmuczerová, Jana and Kozubík, Alois and Machala, Miroslav and Vondráček, Jan}, article_location = {Clare, Ireland}, article_number = {1}, doi = {http://dx.doi.org/10.1016/j.tox.2013.09.001}, keywords = {Inflammation; CYP1B1; Polycyclic aromatic hydrocarbons; Metabolism; DNA adducts}, language = {eng}, issn = {0300-483X}, journal = {Toxicology}, title = {Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cels: the role of enhanced cytochrome P450 1B1 expression}, url = {http://www.sciencedirect.com/science/article/pii/S0300483X13002382}, volume = {314}, year = {2013} }
TY - JOUR ID - 1138900 AU - Šmerdová, Lenka - Neča, Jiří - Svobodová, Jana - Topinka, Jan - Schmuczerová, Jana - Kozubík, Alois - Machala, Miroslav - Vondráček, Jan PY - 2013 TI - Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cels: the role of enhanced cytochrome P450 1B1 expression JF - Toxicology VL - 314 IS - 1 SP - 30-38 EP - 30-38 PB - Elsevier Sci Ireland Ltd SN - 0300483X KW - Inflammation KW - CYP1B1 KW - Polycyclic aromatic hydrocarbons KW - Metabolism KW - DNA adducts UR - http://www.sciencedirect.com/science/article/pii/S0300483X13002382 N2 - Long-term deregulated inflammation represents one of the key factors contributing to lung cancer etiology. Previously, we have observed that tumor necrosis factor-alpha (TNF-alpha), a major pro-inflammatory cytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant INF-alpha, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line. Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levels of both parent B[a]P and its metabolites. INF-alpha altered production of the metabolites associated with dihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNA adducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-alpha also reduced expression of aldo-keto reductase 104, which may compete with CYP1B1 for B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together, the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions. ER -
ŠMERDOVÁ, Lenka, Jiří NEČA, Jana SVOBODOVÁ, Jan TOPINKA, Jana SCHMUCZEROVÁ, Alois KOZUBÍK, Miroslav MACHALA and Jan VONDRÁČEK. Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cels: the role of enhanced cytochrome P450 1B1 expression. \textit{Toxicology}. Clare, Ireland: Elsevier Sci Ireland Ltd, vol.~314, No~1, p.~30-38. ISSN~0300-483X. doi:10.1016/j.tox.2013.09.001. 2013.
|