Adducts of 2-desoxiadenosine and 2-desoxicitydine induced of tetrahydrofuran: structural characterization and detection in DNA / Adutos de 2-desoxiadenosina e 2-desoxicitidina induzidos por tetraidrofurano: caracterização estrutural e detecção em DNA

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

There is a huge concern to identify compounds involved in the development of harmful processes, like cancer. Tetrahydrofuran (THF) is a solvent widely used in industries and recent researches and studies indicated a carcinogenic activity in experimental animals, instigating the investigation of its possible interaction with biomolecules. DNA adducts are used as markers for the identification of genotoxic activity of substances and monitoring the human exposition to genotoxic agents. Studies carried out in vitro, in culture cells and in experimental animals allow to disclose mechanisms and develop methodologies for a posterior evaluation of the human exposition. The continuous development of techniques for the analysis of DNA adducts for biological monitoring constitutes a remarkable concern for the researchers involved with occupational health and preventive medicine. In the present paper, the reaction of THF oxidation products with the nucleosides 2-deoxyadenosine (dAdo) and 2-deoxycitidine (dCyd) were investigated. The structures of the formed adducts were elucidated by mass spectra analysis (ESI/MS-MS) and nuclear magnetic resonance (RMN) after purification of sufficient quantities of the products by high-performance liquid chromatography (HPLC). Thus, the validation of new markers of exposition to THF was made possible. Such damages were detected in DNA incubated with oxidized THF in vitro, after the development of a sensible and selective methodology based on HPLC/ESI/MS-MS. Moreover, mice were exposed to THF vapors and an oxidative damage analysis (8-oxo-2-deoxyguanosine) was carried out on DNA from liver and kidney. An approximate 8-fold increase in the level of 8-oxo-2-deoxyguanosine was observed on DNA from the mices organs exposed to THF. Our in vitro studies indicate the possibility of oxidized THF genotoxic action (formation of adducts with DNA). The occurrence of this path in vivo will be investigated in future studies. In addition, the oxidative damage in target organs of carcinogenesis induced by this solvent was increased.

ASSUNTO(S)

biomarker tetraidrofurano xenobiótico agente tóxico carcinógenos químicos dna xenobiotic biomarcador dna adducts adutos tetrahydrofuran

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