Title of article :
Repair of iron-induced DNA oxidation by the flavonoid myricetin in primary rat hepatocyte cultures
Author/Authors :
Valérie Abalea، نويسنده , , Josiane Cillard، نويسنده , , Marie-Pierre Dubos، نويسنده , , Odile Sergent، نويسنده , , Pierre Cillard، نويسنده , , Isabelle Morel، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 1999
Pages :
10
From page :
1457
To page :
1466
Abstract :
Oxidative DNA damage and its repair in primary rat hepatocyte cultures was investigated following 4 h of incubation with the toxic iron chelate, ferric nitrilotriacetate (Fe-NTA), in the presence or absence of the potent protective flavonoid myricetin (25-50-100 μM). Seven DNA base oxidation products were quantified in DNA extracts by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode. Concomitantly, DNA repair capacity of hepatocytes was estimated by the release of oxidized-base products into culture media, using the same GC-MS method. A genotoxic effect of Fe-NTA (100 μM) in hepatocytes was evidenced by a severe increase in DNA oxidation over basal levels, with accumulation in cellular DNA of five oxidation products derived from both purines and pyrimidines. This prooxidant effect of iron was also noted by an induction of lipid peroxidation, estimated by free malondialdehyde production. Addition of increasing concentrations of myricetin (25-50-100 μM) simultaneously with iron prevented both lipid peroxidation and accumulation of oxidation products in DNA. Moreover, as an activation of DNA repair pathways, myricetin stimulated the release of DNA oxidation bases into culture media, especially of purine-derived oxidation products. This removal of highly mutagenic oxidation products from DNA of hepatocytes might correspond to an activation of DNA excision-repair enzymes by myricetin. This was verified by RNA blot analysis of DNA polymerase β gene expression which was induced by myricetin in a dose-dependent manner. This represented a novel and original mechanism of cytoprotection by myricetin against iron-induced genotoxicity via stimulation of DNA repair processes. Since iron-induced DNA damage and inefficient repair in hepatocytes could be related to genotoxicity and most probably to hepatocarcinogenesis, modulation of these processes in vitro by myricetin might be relevant in further prevention of liver cancer derived from iron overload pathologies.
Keywords :
Hepatocyte culture , free radicals , DNA repair , Flavonoid , Myricetin , DNA damage
Journal title :
Free Radical Biology and Medicine
Serial Year :
1999
Journal title :
Free Radical Biology and Medicine
Record number :
518198
Link To Document :
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