Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA bases by 5‐aminolevulinic acid

FEBS Letters

Bechara, Etelvino J.H²  Di Mascio, Paolo²  Onuki, Janice²  Medeiros, Marisa H.G²  Douki, Thierry¹  Cadet, Jean¹ 

[1] Département de Recherche Fondamentale sur la Matière Condensée, SCIB, Laboratoire `Lésions des Acides Nucléiques', CEA/Grenoble, 17, Avenue des Martyrs, F-38054 Grenoble Cedex 9, France;Departamento de Bioquı́mica, Instituto de Quı́mica, Universidade de São Paulo, CP 26077, CEP 05599-970, São Paulo, Brazil

关键词: DNA damage;    DNA lesion;    5-Aminolevulinic acid;    Hydroxyl radical;    Transition metal;    5-OHCyt;    5-hydroxycytosine;    5-OHdCyd;    5-hydroxy-2′-deoxycytidine;    5-OHdUrd;    5-hydroxy-2′-deoxyuridine;    5-OHUra;    5-hydroxyuracil;    5-ForUra;    5-formyluracil;    5-HMUra;    5-(hydroxymethyl)uracil;    8-oxodAdo;    8-oxo-7;    8-dihydro-2′-deoxyadenosine;    8-oxodGuo;    8-oxo-7;    8-dihydro-2′-deoxyguanosine;    ALA;    5-aminolevulinic acid;    FapyGua;    2;    6-diamino-4-hydroxy-5-formamidopyrimidine;   

DOI  :  10.1016/S0014-5793(98)00504-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

5-Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of which is associated with liver cancer. We show that the reactive oxygen species produced upon ALA metal-catalyzed oxidation promote the formation of several radical-induced base degradation products in isolated DNA. The distribution of modified bases is similar to that obtained upon gamma irradiation. This observation strongly suggests the involvement of hydroxyl radicals in the ALA-mediated DNA damage. Increased levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 5-hydroxy-2′-deoxycytidine in organ DNA of rats chronically treated with ALA were observed. This is strongly suggestive of the implication of hydroxyl radicals in the ALA-induced degradation of cellular DNA.

【 授权许可】

Unknown