Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authorsvan Helden, Yvonne G.J.
Knaapen, Ad M.
Heil, Sandra G.
Briede, Jacob J.
Van Schooten, Frederik J.
Godschalk, Roger W.L.
MetadataShow full item record
Abstractbeta-Carotene (BC) intake has been shown to enhance lung cancer risk in smokers and asbestos-exposed subjects (according to the ATBC and CARET studies), but the mechanism behind this procarcinogenic effect of BC is unclear. Both smoking and asbestos exposure induce an influx of inflammatory neutrophils into the airways, which results in an increased production of reactive oxygen species and formation of promutagenic DNA lesions. Therefore, the aim of our study was to investigate the effects of BC and its metabolites (BCM) on neutrophil-induced genotoxicity. We observed that the BCM vitamin A (Vit A) and retinoic acid (RA) inhibited the H(2)O(2)-utilizing enzyme myeloperoxidase (MPO), which is released by neutrophils, thereby reducing H(2)O(2) conversion. Moreover, BC and BCM were able to increase (.)OH formation from H(2)O(2) in the Fenton reaction (determined by electron spin resonance spectroscopy). Addition of Vit A and RA to lung epithelial cells that were co-incubated with activated neutrophils resulted in a significant increase in the level of oxidized purines assessed by the formamidopyrimidine DNA glycosylase-modified comet assay. These data indicate that BCM can enhance neutrophil-induced genotoxicity by inhibition of MPO in combination with subsequent increased formation of hydroxyl radicals.
CitationFree Radic. Biol. Med. 2009, 46 (2):299-304
JournalFree radical biology & medicine
SponsorsThis study was supported by the European Network of Excellence “Environmental cancer, nutrition and individual susceptibility,” operating within the European Union Sixth Framework Programme, Priority 5: “Food Quality and Safety,” FOOD-CT-2005-513943. Sandra G. Heil and Jaap Keijer were supported by the Dutch Ministry of Agriculture, Nature, and Food Quality.
- Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line.
- Authors: Li H, van Berlo D, Shi T, Speit G, Knaapen AM, Borm PJ, Albrecht C, Schins RP
- Issue date: 2008 Feb 15
- Nitrite enhances neutrophil-induced DNA strand breakage in pulmonary epithelial cells by inhibition of myeloperoxidase.
- Authors: Knaapen AM, Schins RP, Borm PJ, van Schooten FJ
- Issue date: 2005 Sep
- Genotoxic effects of neutrophils and hypochlorous acid.
- Authors: Güngör N, Knaapen AM, Munnia A, Peluso M, Haenen GR, Chiu RK, Godschalk RW, van Schooten FJ
- Issue date: 2010 Mar
- Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung.
- Authors: van Helden YG, Keijer J, Heil SG, Picó C, Palou A, Oliver P, Munnia A, Briedé JJ, Peluso M, Franssen-van Hal NL, van Schooten FJ, Godschalk RW
- Issue date: 2009 Dec
- Mutagenesis by man-made mineral fibres in the lung of rats.
- Authors: Topinka Jb, Loli P, Dusinská M, Hurbánková M, Kováciková Z, Volkovová K, Kazimírová A, Barancoková M, Tatrai E, Wolff T, Oesterle D, Kyrtopoulos SA, Georgiadis P
- Issue date: 2006 Mar 20