Noticia....sobre artigo cientifico

Lesão em DNA induzida por Tetrahidrofurano [THF]
1: Chem Res Toxicol. 2006 Jul 17;19(7):927-936. Links


2'-Deoxyguanosine, 2'-Deoxycytidine, and 2'-Deoxyadenosine Adducts Resulting from the Reaction of Tetrahydrofuran with DNA Bases.


Hermida SAS, Possari EP, Souza DB, Campos IP, Gomes OF, Di Mascio P, Medeiros MH, Loureiro AP.

Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Avenida Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-900, Sao Paulo, Brazil, Programa de Pos-Graduacao em Engenharia de Producao, Instituto de Ciencias Exatas e Tecnologia, Universidade Paulista, Rua Dr. Bacelar 1212, CEP 04026-002, Sao Paulo, Brazil, and Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Avenida Prof. Lineu Prestes 748, CEP 05508-900, Sao Paulo, Brazil.

A 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 NaBH(4) (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/MS-MS. 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.

PMID: 16841961 [PubMed - as supplied by publisher]