Mitochondrial and nuclear DNA damage induced by 5-aminolevulinic acid

5-Aminolevulinic acid (ALA) is a heme precursor accumulated in plasma and in organs in acute intermittent porphyria (AIP), a disease associated with neuromuscular dysfunction and increased incidence of hepatocellular carcinoma (HCC). Liver biopsies of AIP patients showed odd-shaped mitochondria and...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2004-12, Vol.432 (2), p.178-187
Main Authors: Onuki, Janice, Chen, Yiming, Teixeira, Priscila C., Schumacher, Robert I., Medeiros, Marisa H.G., Van Houten, Bennett, Di Mascio, Paolo
Format: Article
Language:English
Subjects:
5-Aminolevulinic acid
Acute intermittent porphyria
Aminolevulinic Acid - pharmacology
Animals
Apoptosis - drug effects
Cell Line
Cell Nucleus - drug effects
Cell Nucleus - ultrastructure
Cell Survival - drug effects
CHO Cells
Cricetinae
DNA - drug effects
DNA - ultrastructure
DNA Damage
Dose-Response Relationship, Drug
Fibroblasts - drug effects
Fibroblasts - ultrastructure
Hepatocellular carcinoma
Hepatocytes - drug effects
Hepatocytes - ultrastructure
Humans
Mitochondria - drug effects
Mitochondria - physiology
Mitochondria - ultrastructure
Mitochondrial DNA damage
PC12 Cells
Quantitative polymerase chain reaction
Rats
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Summary:5-Aminolevulinic acid (ALA) is a heme precursor accumulated in plasma and in organs in acute intermittent porphyria (AIP), a disease associated with neuromuscular dysfunction and increased incidence of hepatocellular carcinoma (HCC). Liver biopsies of AIP patients showed odd-shaped mitochondria and autophagic vacuoles containing well-preserved mitochondria. ALA yields reactive oxygen species upon metal-catalyzed oxidation and causes in vivo and in vitro impairment of rat liver mitochondria and DNA damage. Using a quantitative polymerase chain reaction assay, we demonstrated that ALA induces a dose-dependent damage in nuclear and mitochondrial DNA in human SVNF fibroblasts and rat PC12 cells. CHO cells treated with ALA also show nuclear DNA damage and human HepG2 cells entered in apoptosis and necrosis induced by ALA and its dimerization product, DHPY. The present data provide additional information on the genotoxicity of ALA, reinforcing the hypothesis that it may be involved in the development of HCC in AIP patients.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2004.09.030