Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans.

2.50
Hdl Handle:
http://hdl.handle.net/10146/17401
Title:
Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans.
Authors:
Nair, Urmila; Bartsch, Helmut; Nair, Jagadeesan
Abstract:
Persistent oxidative stress and excess lipid peroxidation (LPO), induced by inflammatory processes, impaired metal storage, and/or dietary imbalance, cause accumulations and massive DNA damage. This massive DNA damage, along with deregulation of cell homeostasis, leads to malignant diseases. Reactive aldehydes produced by LPO, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein, and crotonaldehyde, react directly with DNA bases or generate bifunctional intermediates which form exocyclic DNA adducts. Modification of DNA bases by these electrophiles, yielding promutagenic exocyclic adducts, is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. Ultrasensitive detection methods have facilitated studies of the concentrations of promutagenic DNA adducts in human tissues, white blood cells, and urine, where they are excreted as modified nucleosides and bases. Thus, immunoaffinity-(32)P-postlabeling, high-performance liquid chromatography-electrochemical detection, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, immunoslotblot assay, and immunohistochemistry have made it possible to detect background concentrations of adducts arising from endogenous LPO products in vivo and studies of their role in carcinogenesis. These background adduct levels in asymptomatic human tissues occur in the order of 1 adduct/10(8) and in organs affected by cancer-prone inflammatory diseases these can be 1 or 2 orders of magnitude higher. In this review, we critically discuss the accuracy of the available methods and their validation and summarize studies in which measurement of exocyclic adducts suggested new mechanisms of cancer causation, providing potential biomarkers for cancer risk assessment in humans with cancer-prone diseases.
Citation:
Free Radic. Biol. Med. 2007 43 (8):1109-20
Journal:
Free radical biology & medicine
Issue Date:
15-Oct-2007
URI:
http://hdl.handle.net/10146/17401
DOI:
10.1016/j.freeradbiomed.2007.07.012
PubMed ID:
17854706
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4P7FSCC-3&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=7ec5e7bcfdbe531657f4b158ed4f58cd
Type:
Article
Language:
en
ISSN:
0891-5849
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorNair, Urmila-
dc.contributor.authorBartsch, Helmut-
dc.contributor.authorNair, Jagadeesan-
dc.date.accessioned2008-02-04T10:40:10Z-
dc.date.available2008-02-04T10:40:10Z-
dc.date.issued2007-10-15-
dc.identifier.citationFree Radic. Biol. Med. 2007 43 (8):1109-20en
dc.identifier.issn0891-5849-
dc.identifier.pmid17854706-
dc.identifier.doi10.1016/j.freeradbiomed.2007.07.012-
dc.identifier.urihttp://hdl.handle.net/10146/17401-
dc.description.abstractPersistent oxidative stress and excess lipid peroxidation (LPO), induced by inflammatory processes, impaired metal storage, and/or dietary imbalance, cause accumulations and massive DNA damage. This massive DNA damage, along with deregulation of cell homeostasis, leads to malignant diseases. Reactive aldehydes produced by LPO, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein, and crotonaldehyde, react directly with DNA bases or generate bifunctional intermediates which form exocyclic DNA adducts. Modification of DNA bases by these electrophiles, yielding promutagenic exocyclic adducts, is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. Ultrasensitive detection methods have facilitated studies of the concentrations of promutagenic DNA adducts in human tissues, white blood cells, and urine, where they are excreted as modified nucleosides and bases. Thus, immunoaffinity-(32)P-postlabeling, high-performance liquid chromatography-electrochemical detection, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, immunoslotblot assay, and immunohistochemistry have made it possible to detect background concentrations of adducts arising from endogenous LPO products in vivo and studies of their role in carcinogenesis. These background adduct levels in asymptomatic human tissues occur in the order of 1 adduct/10(8) and in organs affected by cancer-prone inflammatory diseases these can be 1 or 2 orders of magnitude higher. In this review, we critically discuss the accuracy of the available methods and their validation and summarize studies in which measurement of exocyclic adducts suggested new mechanisms of cancer causation, providing potential biomarkers for cancer risk assessment in humans with cancer-prone diseases.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4P7FSCC-3&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=7ec5e7bcfdbe531657f4b158ed4f58cden
dc.subjectlipid peroxidationen
dc.subjectExocyclic etheno-, Propano-, Malondialdehyde adductsen
dc.subjectDNA adductsen
dc.subject.meshAdenine-
dc.subject.meshAnimals-
dc.subject.meshBiological Markers-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Damage-
dc.subject.meshDeoxyadenosines-
dc.subject.meshDeoxyguanosine-
dc.subject.meshHumans-
dc.subject.meshInflammation-
dc.subject.meshLipid Peroxidation-
dc.subject.meshMalondialdehyde-
dc.subject.meshNeoplasms-
dc.titleLipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans.en
dc.typeArticleen
dc.identifier.journalFree radical biology & medicineen

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