The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells.
The effects of the flavonoids quercetin, myricetin and silymarin on DNA damage and cytotoxicity in human cells were investigated. DNA strand breaks and oxidised pyrimidines were determined using alkaline single cell gel electrophoresis (the comet assay). Inhibition of cell growth was also measured. Caco-2 (colon), HepG2 (liver), HeLa (epithelial) cells and normal human lymphocytes showed different, dose-dependent susceptibilities (in terms of strand breakage) to the various flavonoids, quercetin being the most damaging. This agreed well with the ability of the flavonoids to inhibit cell growth. None of the flavonoids induced DNA base oxidation above background levels. All of the flavonoids under investigation caused depletion of reduced glutathione, which, in the case of quercetin, occurred prior to cell death. Neither cytotoxicity nor genotoxicity was associated with the antioxidant enzyme capacity (glutathione, glutathione reductase, glutathione peroxidase and catalase) of the cells.
Duthie
S J
SJ
Rowett Research Institute, Bucksburn, Aberdeen, UK.
Johnson
W
W
Dobson
V L
VL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005419:Flavonoids; D011743:Pyrimidines; D012838:Silymarin; C040015:myricetin; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione