Role of quercetin on mitomycin C induced genotoxicity: analysis of micronucleus and chromosome aberrations in vivo.

Quercetin, a flavonol group of plant flavonoid, has generated immense interest because of its potential antioxidant, anti-proliferative, chemoprotective, anti-inflammatory and gene expression modulating properties. However, the pro-oxidant chemistry of quercetin is important as it is related to the generation of mutagenic quinone-type metabolites. In the present study, 25mg/kg, 50mg/kg and 100mg/kg of quercetin given through the intra peritoneal (i.p.) route induced 2.31 ± 0.27%, 4.72 ± 0.58% and 6.38 ± 0.68% (control value=0.67 ± 0.30%) respectively, of cells with micronucleus (MN) in polychromatic erythrocytes in bone marrow cells and 10.93 ± 0.98%, 10.00 ± 0.89% and 14.27 ± 3.94% (control 2.61 ± 0.48) of cells with chromosome aberrations (CA) following 24h of the treatments. Higher frequencies of MN and CA were also observed after 48h of the treatments. To verify the effect of route of treatment on the quercetin induced damage, 100mg/kg b.w. was given through oral route which declined frequency of MN (P<0.001) as well as CA (P<0.05) as compared to the i.p. route for the same dose. Quercetin also induced higher frequency of metaphases with sticky chromosomes and C-mitosis. Pre-treatment with quercetin significantly reduced the frequency of mitomycin C (MMC) induced MN as well as CA, but no clear correlation between the dose and effect could be observed. Further studies are required to elucidate the possible interaction of quercetin with DNA as well as with other DNA damaging agents like MMC in vivo. The protective action of quercetin was not enhanced when given orally. Our findings suggest that quercetin may result in genomic instability in the tested dose range and significant reduction in MMC induced genotoxicity in the highest dose tested. These effects of quercetin are to be taken into consideration while evaluating the possible use of quercetin as a therapeutic agent.

Micronucleus and other nuclear abnormalities among betel quid chewers with or without sadagura, a unique smokeless tobacco preparation, in a population from North-East India.

Genotoxicity is one of the important endpoints for risk assessment of various lifestyle factors. The study is the first report on the genotoxic effect associated with sadagura, a unique smokeless tobacco prepared in southern Assam province of North-East India. Sadagura is consumed with or without betel quid and/or smoking. In the present cytogenetic monitoring study, analysis of micronuceus (MN), nuclear bud, binucleated, karyorrhectic, karyolytic and pyknotic cells tests were performed in the exfoliated buccal cells of 75 habituates and compared to controls matched for gender, age, and habit. Significant increase in the frequency of MN was found in sadagura chewers (0.48%, P < 0.001), smokers (0.46%, P < 0.01), betel quid with sadagura chewers (0.91%, P < 0.001) and smokers chewing betel quid with sadagura (0.53%, P < 0.001) as compared to the unexposed control group (0.07%). Betel quid chewers showed significant increase (1.65%, P < 0.05) in the frequency of binucleated cells as compared to the control group (0.16%). Results of this study demonstrated that sadagura consumed as a single agent or in combination with betel quid, leads to a significant induction of cytogenetic damage in the buccal epithelial cells of habituates. We suggest that analysis of other degenerative nuclear changes in addition to MN can provide valuable information while evaluating potential genotoxic agents.

Effects of low dose radiation and vitamin C treatment on chloroquine-induced genotoxicity in mice.

Chloroquine (CHQ) is a commonly used antimalarial agent. We evaluated the genotoxic potential of CHQ using chromosome aberration (CA), micronucleus (MN), and sperm head abnormality (SA) assays in vivo in Swiss albino mice. The interaction between a low dose of radiation and CHQ, as well as the effect of vitamin C on CHQ-induced genotoxicity, was also evaluated. It was observed that CHQ induced CA, as well as MN, in the bone marrow cells under certain treatment conditions. Further, CHQ induced significant increase in the frequency of SA both at 24 hr and 21 days of the treatment. In the present study vitamin C pretreatment apparently reduced the frequency of CA, MN, and SA induced by CHQ. In the combination studies with radiation and CHQ, we found that exposure to low doses of radiation (0.5 Gy) either prior to or following CHQ treatment, in the dose ranges tested, has little or no synergistic effect in the mutagenic evaluations in somatic cells. However, radiation exposure along with CHQ treatment resulted in significant increase in the frequency of SA as compared to the groups receiving CHQ alone at 21 days of the treatment. In summary, CHQ has the potential to induce genotoxicity in mammalian cells. Further, germ cells may be relatively more sensitive as compared to the somatic cells.