This study was conducted to elucidate the in vitro protective effect of five flavonoids [apigenin (1), apigenin-7-O-glucoside (2), centaureidin (3), jaceidin (4) and quercetin (5)] against chromosomal damage in mitogen-induced human lymphocytes. Using the Cytochalasin-B blocked micronucleus (CBMN) assay, in which the biomarker of chromosome breakage and/or chromosome loss is the elevated frequency of micronucleus (MN) in binucleated (BN) cells, the presence of flavonoid 2 in minimal concentration (3 μg/mL) gave a 35.5% decrease in the frequency of MN when compared with control human lymphocytes. The same concentration of flavonoids 1, 3 and 4, reduced the MN frequency by 24.4%, 28.0% and 28.0%, respectively. Higher concentrations (6 μg/mL and 10 μg/mL) seemed less effective. Flavonoid 5 (3 μg/mL) induced a slight decrease in MN frequency (5%), while higher doses (6 μg/mL and 10 μg/mL) provoked an increase of DNA damage. The comparable values for the cytokinesis-block proliferation index (CBPI) of the tested flavonoids and positive control suggested an inhibitory effect on lymphocyte proliferation. In the DPPH. scavenging assay, flavonoids 1-4 demonstrated modest activity, in a dose-dependent manner, compared with the synthetic antioxidants BHT and Trolox, while 5 exhibited comparably high antioxidative activity.
SaijaA, ScaleseM, LanzaM, MarzulloD, BoninaF, CastelliF. (1995) Flavonoid as antioxidant agents: importance of their interaction with biomembranes. Free Radical Biology & Medicine, 19, 481–486;
2.
NijveldtJR, van NoodE, van HoornECD, BoelensGP, van NorrenK, van LeeuwenAMP. (2001) Flavonoids: a review of probable mechanisms of action and potential applications. American Journal of Clinical Nutrition, 74, 418–425;
3.
MiglioreL, TestaA, ScarpatoR, PaveseN, PetrozziL, BonuccelliU. (1997) Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease. Human Genetics, 101, 299–305;
4.
PetrozziL, LucettiC, GambacciniG, BernardiniS, Del DottoP, MiglioreL, ScarpatoR, BonuccelliU. (2001) Cytogenetic analysis oxidative damage in lymphocytes of Parkinson's disease patients. Neurological Science, 22, 83–84;
5.
ScappaticciS, ForaboscoA, BorroniG, OrecchiaG, FraccaroM. (1990) Clonal structural chromosomal rearrangements in lymphocytes of four patients with Werner's syndrome. Annales de genetique, 33, 5–8;
6.
FenechM, MorleyAA. (1985) Measurement of micronuclei in lymphocytes. Mutation Research, 147, 29–36;
7.
FenechM, MorleyAA. (1991) Optimization of micronucleus assay for biological dosimetry. Progress in Clinical Biological Research, 372, 373–386.
8.
AljancićI., VajsV, MenkovićN, KaradzićI, JuranićN, MilosavljevićS, MacuraS. (1999) Flavones and sesquiterpene lactones from Achillea atrata subsp. multifida: antimicrobial activity. Journal of Natural Products, 62, 909–911;
RithidechKN, TungjaiM, WhortonEB. (2005) Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes. Mutation Research, 585, 96–104;
11.
NoelS, KasinathanM, RathKS. (2006) Evaluation of apigenin using in vitro cytochalasin blocked micronucleus assay. Toxicology in Vitro, 20, 1168–1172.
12.
SaitoA, SugisawaA, UmegakiK, Sunagawa. (2004) .Protective effects of quercetin and its metabolites on H2O2-induced chromosomal damage to WIL2-NS cells. Bioscience, Biotechnology, and Biochemistry, 68, 271–276;
13.
UmegakiK, FenechM. (2000) Cytokinesis-block micronucleus assay in WIL2-NS cells: a sensitive system to detect chromosomal damage induced by reactive oxygen species and activated human neutrophils. Mutagenesis, 15, 261–269;
14.
GođevacD, VujisićLj, MojovićM, IgnjatovićA, SpasojevićI, VajsV. (2008) Evaluation of antioxidant capacity of Allium ursinum L. volatile oil and its effect on membrane fluidity. Food Chemistry, 107, 1692–1700;
15.
Rice-EvansCA, MillerNJ. (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biology and Medicine, 20, 933–56;
16.
FenechM, MorleyAA. (1993) The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutation Research, 285, 35–44;
17.
SurrallesJ, XamenaN, CreusA, CatalanJ, NorppaH, MarcosR. (1995) Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures. Mutation Research, 341, 169–184;
18.
BloisMS. (1958) Antioxidant determinations by the use of a stable free radical. Nature, 181, 119–1200.
