Susceptibility of lung epithelial cells to alkylating genotoxic insult
| Autor: | Róza Ádány, Károly Nagy, Sándor Szucs, Balázs Ádám |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Ethylene Oxide
Keratinocytes Alkylating Agents Chromatography Gas Alkylation media_common.quotation_subject Toxicology Epithelial Cells/drug effects Insult Hydrogen Peroxide/toxicity medicine Humans Ethylene Oxide/toxicity DNA/drug effects Mutagens/toxicity Lung Alkylating Agents/toxicity Cells Cultured Keratinocytes/chemistry media_common Leukocytes Mononuclear/drug effects business.industry Lung/chemistry Epithelial Cells DNA Hydrogen Peroxide General Medicine medicine.anatomical_structure DNA Damage/drug effects Leukocytes Mononuclear Linear Models Cancer research Comet Assay business DNA Damage Mutagens |
| Zdroj: | Nagy, K, Ádány, R, Szűcs, S & Ádám, B 2013, ' Susceptibility of lung epithelial cells to alkylating genotoxic insult ', Environmental and Molecular Mutagenesis, vol. 54, no. 8, pp. 682-689 . https://doi.org/10.1002/em.21800 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2014.06.290 |
| Popis: | Alkylation is one of the most common types of DNA damage that can lead to mutations and cancer. Lung is the primary target organ of airborne alkylators such as ethylene oxide (EO). However, the ability of EO to cause lung cancer has not been clearly demonstrated yet. The aim of this study was to investigate the susceptibility of lung cells to alkylating DNA insult by detecting EO-mediated DNA damage with the alkaline comet assay in human lung epithelial cells, peripheral blood lymphocytes, and keratinocytes. The susceptibility of these cell types toward the alkylating insult induced by EO was compared against the oxidative DNA insult induced by hydrogen peroxide (H 2O 2). Due to the volatility of EO, its active concentrations were monitored by gas chromatography during exposure and were found to decrease significantly in a time-dependent manner. EO induced a statistically significant genotoxic effect at the lowest concentration used (16.4 μM) in lung epithelial cells and in lymphocytes, while in keratinocytes, a genotoxic effect was not detected until 55.5 μM EO. However, lung epithelial cells demonstrated increased resistance to oxidative insult. In fact, oxidative DNA damage detectable by endonuclease treatment was minimal in lung cells compared with the other cell types. These results suggest an increased sensitivity of lung epithelial cells toward the alkylating effects of EO, which was not observed for oxidative DNA damage. Our findings point out the importance of DNA alkylation and the possible role of EO on the induction of lung cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect