5-aminolevulinic acid (ALA) is the first precursor of heme biosynthetic pathway.  This compound has widely been used in photodynamic therapy (PDT) as a precursor of protoporphyrin IX, and efficient photosensitizer (PpIX), which is accumulated preferencially in tumoral cells.  ALA is usually topically applied in skin cancer and in the diagnosis of tumors of skin, spleen, gastrointestinal tract and lung.  The porphyrias are inherited or acquired diseases in which occurs an enzyme deficiency of the heme biosynthetic pathway.  This deficiency leads to excessive production and excretion of porphyrins and its precursors.  We are particularly interest in the porphyrias in which occurs an increase of ALA: acute intermittent porphyria, tyrosinosis and lead poisoning.  It has been demonstrated that ALA can undergo metal-catalyzed oxidation producing reactive oxygen species and the aldehyde, 4, 5- dioxovaleric acid (DOVA).  ALA could also dimerize to form dihydropyrazine derivatives (DHPY), which in the presence of copper could also produce ROS.  ALA was able to damage plasmid, calf thymus DNA and mitochondrial  DNA in vitro, to increase the steady state level of 8-oxo-7,8-dihydro-2’-deoxyguanosine and 5-hydroxy-2’-deoxycytidine in liver DNA of ALA- treated rats.  Formation of hydroxyl radical-induced modified DNA bases was also detected in calf thymus DNA.  DOVA was able to produce DNA strand breaks and induce alkylation of the guanine moieties within both nucleoside and isolated DNA.  ALA and DOVA showed to be mutagenic in Salmonella/microsome mutagenicity assay and SOS Chromotest.  The ALA dimerization product, 3, 6-dihydropyrazine-2, 5-dipropanoic acid also produced strand breaks and increase in 8-oxodGuo.  These results suggest that ALA and DOVA have mutagenic potential that may contribute to an increased frequency of hepatocellular carcinoma in patients with acute intermittent porphyria and tyrosinosis, and have also to be considered in the PDT.