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. Toxicology. Clare, Ireland: Elsevier Sci Ireland Ltd, 2013, vol. 314, No 1, p. 30-38. ISSN 0300-483X. doi:10.1016/j.tox.2013.09.001.
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Basic information
Original name Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cels: the role of enhanced cytochrome P450 1B1 expression
Name in Czech Zánětlivé mediátory urychlují metabolismus benzo[a]pyrenu v potkaních alveolárních buňkách typu II : role zvýšené exprese cytochromu P450 1B1
Authors ŠMERDOVÁ, Lenka (203 Czech Republic), Jiří NEČA (203 Czech Republic), Jana SVOBODOVÁ (203 Czech Republic, belonging to the institution), Jan TOPINKA (203 Czech Republic), Jana SCHMUCZEROVÁ (203 Czech Republic), Alois KOZUBÍK (203 Czech Republic), Miroslav MACHALA (203 Czech Republic) and Jan VONDRÁČEK (203 Czech Republic).
Edition Toxicology, Clare, Ireland, Elsevier Sci Ireland Ltd, 2013, 0300-483X.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30104 Pharmacology and pharmacy
Country of publisher Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.745
RIV identification code RIV/00216224:14310/13:00081939
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1016/j.tox.2013.09.001
UT WoS 000209429700004
Keywords (in Czech) Zánět, CYP1B1; Polycyklické aromatické uhlovodíky, Metabolismus, DNA adukty
Keywords in English Inflammation; CYP1B1; Polycyclic aromatic hydrocarbons; Metabolism; DNA adducts
Tags AKR, rivok
Tags International impact, Reviewed
Changed by Changed by: Ing. Andrea Mikešková, učo 137293. Changed: 5. 5. 2016 10:37.
Abstract
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.
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