06 Jan 2005 04:51
Ochratoxin A-induced DNA damage in human
1: J Nutr Biochem. 2005 Jan;16(1):31-7.
Ochratoxin A-induced DNA damage in human fibroblast: protective
effect of cyanidin 3-O-beta-d-glucoside.
Russo A, La Fauci L, Acquaviva R, Campisi A, Raciti G, Scifo C,
Renis M, Galvano G, Vanella A, Galvano F.
Department of Biochemistry, Medical Chemistry and Molecular
Biology, University of Catania, Catania 95100, Italy.
Ochratoxin A (OTA), a mycotoxin produced by Aspergillus
ochraceus and other moulds, has recently received growing
attention because of its carcinogenic, teratogenic and
nephrotoxic properties in both humans and farm animals.
Nevertheless, with regard to the mechanism of toxicity, the data
in the literature are inconclusive. The aim of our work was to
verify in human fibroblasts treated with different OTA dosages
the involvement of oxidative pathway in the damage mechanism of
this mycotoxin and the possible protective effect exerted by
cyanidin 3-O-beta-d-glucoside (C3G), an anthocyanin present in
pigmented oranges, red wines, fruits and vegetables. The
addition of OTA at 25 and 50 muM concentrations for 48 h
determined only a slight but significant (P<.05) increase in
radical oxygen species, whereas a substantial increase in their
production was observed at longer exposure, in particular, when
the fibroblasts were treated with 50 muM OTA for 72 h. Under the
same experimental conditions, our data showed a significant
(P<.05) increase in the rupture of cellular membrane and high
damage to genomic DNA, evaluated by single-cell gel
electrophoresis (comet assay), thus confirming the involvement
of oxidative stress in the OTA genotoxicity in agreement with
other studies. Diversely, mitochondrial functionality does not
appear influenced by OTA treatment. C3G (0.125, 0.250 mM) added
to the cells treated with 50 muM OTA significantly reduced free
radical species production and prevented genomic DNA damage.