Increased genotoxic susceptibility of breast epithelial cells to ethylene oxide.
This study was carried out with the aim of elucidating the organ-specific effects of ethylene oxide in comparison with the sensitivity of cells from different tissues. An increased incidence of leukemia and lymphoma has been observed in workers exposed to ethylene oxide. However, contradictory findings exist regarding its ability to induce other tumor types, such as breast cancer. We characterized the genotoxicity of ethylene oxide by means of the alkaline version of comet assay in in vitro systems, in order to investigate the hypothesized role of this substance in the development of breast cancer. For this study, we used primary and secondary cultures of lymphoblasts (well-known target cells of the genotoxicity of ethylene oxide), breast epithelial cells (hypothesized target), peripheral blood lymphocytes (cells commonly used in biomonitoring), and of keratinocytes and cervical epithelial cells. DNA damage was measured and expressed as tail DNA, tail length, and tail moment. In the concentration range 0-100 microM, ethylene oxide induced a dose-dependent increase of DNA damage in the investigated cell types without notable cytotoxicity. A statistically significant increase of DNA damage could be observed after treatment with 20 microM ethylene oxide in lymphoblasts (51% increase of tail moment over the background), breast epithelial cells (26% increase) and peripheral lymphocytes (71% increase). In keratinocytes (5% increase) and cervical epithelial cells (5% increase) significant DNA damage could not be detected at this dose, but at higher concentrations (50-100 microM), such an increase was observed. These results are indicative of an increased sensitivity of breast epithelial cells towards genotoxic insults of ethylene oxide. Our observations provide additional data to evaluate the hypothesis that exposure to ethylene oxide may play a role in breast cancer, and the findings may contribute to the development of screening tests for monitoring an early response to genotoxic insults in occupational settings.
Adám
Balázs
B
Department of Preventive Medicine, School of Public Health, Medical and Health Science Center, University of Debrecen, P.O. Box 9, H-4012, Debrecen, Hungary.
Bárdos
Helga
H
Adány
Róza
R
D001940:Breast / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005027:Ethylene Oxide / Q000633:toxicity*; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D009153:Mutagens / Q000633:toxicity; D009928:Organ Specificity
D009153:Mutagens; D005027:Ethylene Oxide