Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA bases by 4-aminolevulinic acid

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. (C) 1998 Federation of European Biochemical Societies.