Glutathione depletion by buthionine sulfoximine induces oxidative damage to DNA in organs of rabbits in vivo

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dc.contributor.authorGokce G.
dc.contributor.authorOzsarlak-Sozer G.
dc.contributor.authorOktay G.
dc.contributor.authorKirkali G.
dc.contributor.authorJaruga P.
dc.contributor.authorDizdaroglu M.
dc.contributor.authorKerry Z.
dc.date.accessioned2019-10-27T08:35:43Z
dc.date.available2019-10-27T08:35:43Z
dc.date.issued2009
dc.departmentEge Üniversitesien_US
dc.description.abstractGlutathione (GSH) exists in mammalian tissues in vivo at high concentrations and plays an important protective role against oxidatively induced damage to biological molecules, including DNA. We investigated oxidatively induced damage to DNA by GSH depletion in different organs of rabbits in vivo. Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), an effective GSH-depleting compound. GSH levels were measured in heart, brain, liver, and kidney of animals. BSO treatment significantly reduced GSH levels in heart, brain, and liver, but not in kidney. DNA was isolated from these tissues to test whether GSH depletion causes oxidatively induced DNA damage in vivo. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry with isotope dilution methods were applied to measure typical products of oxidatively induced damage in isolated DNA samples. Several such products were identified and quantified in all organs. BSO treatment caused significant formation of 8-hydroxyguanine, 2,6-diamino-4- hydroxy-5-formamidopyrimidine, 8-hydroxyadenine, and (5'S)-8,5'- cyclo-2'-deoxyadenosine in DNA of organs of rabbits. Animals were fed with the semiessential amino acid 2-aminoethanesulfonic acid (taurine) during BSO treatment. Taurine significantly inhibited GSH depletion and also formation of DNA products. Depletion of GSH correlated well with formation of DNA products, indicating the role of GSH in preventing oxidatively induced DNA damage. Our findings might contribute to the understanding of pathologies associated with DNA damage, oxidative stress, and/or defective antioxidant responses and improve our understanding of the effect of BSO in increasing the efficacy of anticancer therapeutics. © 2009 American Chemical Society.en_US
dc.identifier.doi10.1021/bi900030zen_US
dc.identifier.endpage4987en_US
dc.identifier.issn0006-2960
dc.identifier.issue22en_US
dc.identifier.pmid19374446en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage4980en_US
dc.identifier.urihttps://doi.org/10.1021/bi900030z
dc.identifier.urihttps://hdl.handle.net/11454/27283
dc.identifier.volume48en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.relation.ispartofBiochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.titleGlutathione depletion by buthionine sulfoximine induces oxidative damage to DNA in organs of rabbits in vivoen_US
dc.typeArticleen_US

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