Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells.

2.50
Hdl Handle:
http://hdl.handle.net/10146/83695
Title:
Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells.
Authors:
van Helden, Yvonne G.J.; Keijer, Jaap; Knaapen, Ad M.; Heil, Sandra G.; Briede, Jacob J.; Van Schooten, Frederik J.; Godschalk, Roger W.L.
Abstract:
beta-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.
Citation:
Free Radic. Biol. Med. 2009, 46 (2):299-304
Journal:
Free radical biology & medicine
Issue Date:
15-Jan-2009
URI:
http://hdl.handle.net/10146/83695
DOI:
10.1016/j.freeradbiomed.2008.10.038
PubMed ID:
19026740
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4TTHWBC-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=39e2ec6ab501a2152208eb021206c8e4
Type:
Article
Language:
en
ISSN:
1873-4596
Sponsors:
This 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.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorvan Helden, Yvonne G.J.en
dc.contributor.authorKeijer, Jaapen
dc.contributor.authorKnaapen, Ad M.en
dc.contributor.authorHeil, Sandra G.en
dc.contributor.authorBriede, Jacob J.en
dc.contributor.authorVan Schooten, Frederik J.en
dc.contributor.authorGodschalk, Roger W.L.en
dc.date.accessioned2009-10-07T07:33:31Z-
dc.date.available2009-10-07T07:33:31Z-
dc.date.issued2009-01-15-
dc.identifier.citationFree Radic. Biol. Med. 2009, 46 (2):299-304en
dc.identifier.issn1873-4596-
dc.identifier.pmid19026740-
dc.identifier.doi10.1016/j.freeradbiomed.2008.10.038-
dc.identifier.urihttp://hdl.handle.net/10146/83695-
dc.description.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.en
dc.description.sponsorshipThis 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.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4TTHWBC-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=39e2ec6ab501a2152208eb021206c8e4en
dc.subjectMyeloperoxidaseen
dc.subjectβ-Caroteneen
dc.subjectVitamin Aen
dc.subjectRetinolen
dc.subjectRetinalen
dc.subjectRetinoic aciden
dc.subjectLungen
dc.subjectCarcinogenesisen
dc.subjectESRen
dc.subjectEPRen
dc.subjectFPG cometen
dc.subjectVitamin Een
dc.subjectα-Tocopherolen
dc.subjectSuperoxide anionen
dc.subjectHydroxyl radicalen
dc.subjectInflammationen
dc.subjectFree radicalsen
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Movement-
dc.subject.meshDNA Damage-
dc.subject.meshElectron Spin Resonance Spectroscopy-
dc.subject.meshEpithelial Cells-
dc.subject.meshHumans-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshInflammation-
dc.subject.meshInflammation Mediators-
dc.subject.meshLung-
dc.subject.meshMutagenicity Tests-
dc.subject.meshNeutrophil Activation-
dc.subject.meshNeutrophils-
dc.subject.meshOxidation-Reduction-
dc.subject.meshOxidative Stress-
dc.subject.meshPeroxidase-
dc.subject.meshPurines-
dc.subject.meshTretinoin-
dc.subject.meshVitamin A-
dc.subject.meshbeta Carotene-
dc.titleBeta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells.en
dc.typeArticleen
dc.identifier.journalFree radical biology & medicineen

Related articles on PubMed

All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.