2 '-Deoxyguanosine, 2 '-deoxycytidine, and 2 '-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorHermida, Silvia A. S.
dc.creatorPossari, Ediliz P. M.
dc.creatorSouza, Denise B.
dc.creatorArruda Campos, Ivan P. de
dc.creatorGomes, Osmar F.
dc.creatorDi Mascio, Paolo
dc.creatorMedeiros, Marisa H. G.
dc.creatorLoureiro, A. Paula M.
dc.date2015-03-18T15:54:15Z
dc.date2016-10-25T20:28:11Z
dc.date2015-03-18T15:54:15Z
dc.date2016-10-25T20:28:11Z
dc.date2006-07-17
dc.date.accessioned2017-04-06T07:08:06Z
dc.date.available2017-04-06T07:08:06Z
dc.identifierChemical Research In Toxicology. Washington: Amer Chemical Soc, v. 19, n. 7, p. 927-936, 2006.
dc.identifier0893-228X
dc.identifierhttp://hdl.handle.net/11449/116842
dc.identifierhttp://acervodigital.unesp.br/handle/11449/116842
dc.identifier10.1021/tx060033d
dc.identifierWOS:000239039600007
dc.identifierhttp://dx.doi.org/10.1021/tx060033d
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/927489
dc.descriptionA recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH4 ( the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MSMS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/ microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.
dc.languageeng
dc.publisherAmer Chemical Soc
dc.relationChemical Research In Toxicology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.title2 '-Deoxyguanosine, 2 '-deoxycytidine, and 2 '-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases
dc.typeOtro


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