AhR-dependent regulation of transcriptome and phenotypic manifestation of human bronchial epithelial cells during chemical transformation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000213" target="_blank" >RIV/00027162:_____/20:N0000213 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

AhR-dependent regulation of transcriptome and phenotypic manifestation of human bronchial epithelial cells during chemical transformation

Original language description

Polycyclic aromatic hydrocarbons (PAHs) and their derivatives belong among principle air pollutants, which elicit both genotoxic and non-genotoxic effects. One of the most studied carcinogenic PAHs is benzo[a]pyrene (BaP), a potent agonist of the aryl hydrocarbon receptor (AhR), which plays an important role in many processes associated with cancer promotion and/or progression. In our study, functional annotation of microarray datasets analyzed in normal human bronchial epithelial HBEC-12KT cells before and after their continuous exposure to BaP (1 uM) for 12 weeks (HBEC-12KT-B1 cell line) was performed to determine significant change in pathways/biological processes induced during the chemical cell transformation. Moreover, both HBEC-12KT and HBEC-12KT-B1 cells were exposed to BaP and prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for short (24-72 hours) and prolonged (2 weeks) time intervals to compare responses of the non-transformed and transformed epithelial airway cells. Both transcriptome analysis and the phenotypic changes occurring during epithelial-to-mesenchymal transition (EMT) or cell transformation process, including cell morphology, cell cycle distribution, cell proliferation and migration potential were investigated during further experiments. Two-week exposure to BaP or TGF- (used as a positive control for EMT induction) led to a significant inhibition of both HBEC-12KT and HBEC-12KT-B1 cell proliferation connected with cell cycle arrest, while TCDD had no effect. Next, we evaluated the effects of two-week exposure to BaP, TCDD or TGF- on EMT induction. While HBEC-12KT cells exposed to TCCD exhibited epithelial morphology, the cells exposed to BaP or TGF- acquired an elongated, fibroblast-like shape, thus like morphology of HBEC-12KT-B1 cells. However, the migration ability of the non-transformed cells remained insignificant after the two week exposure. On the other hand, prolonged exposure to BaP or TGF- enhanced motility of transformed HBEC-12KT-B1 cells, which correspond to our recent study with A549 cells.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

<a href="/en/project/GA19-25365S" target="_blank" >GA19-25365S: The mechanisms of carcinogenic processes in normal and transformed airway cellular models exposed to airborne aromatic toxicants</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů