Apoptotic gene expression profiles and DNA damage levels in rat liver treated with perfluorooctane sulfonate and protective role of curcumin.

Perfluorinated compounds (PFCs) such as PFOS and PFOA, are xenobiotics that can be detected worldwide in the environment and humans. PFOS (C8F17SO3-) is a fluorinated organic compound has been used for decades in industrial and commercial products. We investigated the genotoxic and apoptotic impact of PFOS in rat liver using comet assay, micronucleus test and apoptotic gene expression methods for caspase 3, caspase 8 and the protective role of curcumin on the PFOS- induced damage under chronic exposure. In this study, rats were treated either with three different PFOS doses only (0.6, 1.25 and 2.5mg/kg) or one dose of curcumin (80mg/kg) or three different doses of PFOS combined with 80mg/kg dose of curcumin by gavage for 30days at 48h intervals. We evaluated the DNA damage via comet assay and micronucleus test. Doses of PFOS increased micronucleus frequency (p<0.05) and strongly induced DNA damage in liver in two different parameters; i: the damaged cell percentage and ii: genetic damage index. Curcumin prevented the formation of DNA damage induced by PFOS and curcumin substance applied with PFOS caused a decrease in the micronucleus frequency. PFOS increased apoptotic gene expression but curcumin decreased the expression levels of caspase 3 and 8.

Curcumin prevents perfluorooctane sulfonate-induced genotoxicity and oxidative DNA damage in rat peripheral blood.

Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and global pollutant. PFOS a persistent and bioaccumulative compound, and it is widely distributed in humans and wildlife. Therefore, it was added to Annex B of the Stockholm Convention on Persistent Organic Pollutants in May 2009. Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric. It is commonly used as a dietary spice and coloring agent in cooking and anecdotally as an herb in traditional Asian medicine. In this study, male rats were treated with three different PFOS doses (0.6, 1.25, and 2.5 mg/kg) and one dose of curcumin, from Curcuma longa (80 mg/kg), and combined three doses of PFOS with 80 mg/kg dose of curcumin by gavage for 30 d at 48 h intervals. Here, we investigated the DNA damage via single-cell gel electrophoresis/comet assay and micronucleus test in rat peripheral blood in vivo. It is found that all doses of PFOS increased micronucleus frequency (p < 0.05) and strongly induced DNA damage in peripheral blood in two different parameters; the damaged cell percent and genetically damage index, and curcumin prevented the formation of DNA damage induced by PFOS. Results showed that curcumin inhibited DNA damage including GDI at certain levels at statistical manner, 30.07%, 54.41%, and 36.99% for 0.6 mg/kg, 1.25 mg/kg, and 2.5 mg/kg.

The protective role of curcumin on perfluorooctane sulfonate-induced genotoxicity: single cell gel electrophoresis and micronucleus test.

Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and global pollutant. PFOS a persistent and bioaccumulative compound, is widely distributed in humans and wildlife. Therefore, it was added to Annex B of the Stockholm Convention on Persistent Organic Pollutants in May 2009. Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric. It is commonly used as a dietary spice and coloring agent in cooking and anecdotally as an herb in traditional Asian medicine. In this study, male rats were treated with three different PFOS doses (0.6, 1.25 and 2.5 mg/kg) and one dose of curcumin, from Curcuma longa (80 mg/kg) and combined three doses of PFOS with 80 mg/kg dose of curcumin by gavage for 30 days at 48 h intervals. Here, we evaluated the DNA damage via single cell gel electrophoresis or comet assay and micronucleus test in bone marrow in vivo. PFOS induced micronucleus frequency and decreased the ratio of polychromatic erythrocyte to normochromatic erythrocyte in bone marrow. Using the alkaline comet assay, we showed that all doses of the PFOS strongly induced DNA damage in rat bone marrow and curcumin prevented the formation of DNA damage induced by PFOS.

Assessment of genetic damage in buccal epithelium cells of painters: micronucleus, nuclear changes, and repair index.

The micronucleus (MN) assay in exfoliated buccal cells is a useful and minimally invasive method for monitoring genetic damage in humans exposed to occupational and environmental agents. The MN test is used as an indicator of genotoxic exposition, since it is associated with chromosome aberrations. An increased mutation rate in oral squamous cells, which is indicated by an increased MN frequency, is also related to the development of oral mucosa diseases, such as carcinomas. We evaluated MN frequencies and other nuclear changes (NCs), karyorrhexis (KR), karyolysis (KL), broken egg (BE), and binucleus in buccal mucosa cells of 60 painters (30 smokers and 30 nonsmokers) and 60 healthy control subjects (30 smoker and 30 nonsmoker). Microscopic observation of 3000 cells per individual was performed in both painters and control subjects. In the control group and the exposed group, for each person repair index (RI) was calculated via the following formula: (KR + KL)/(BE + MN). The results showed a statistically significant increase in the frequency of MN in buccal epithelial cells of the exposed group compared with the control group (p < 0.05). Smokers and nonsmokers differed with respect to the incidence of MN and NCs in all groups. In painters, RI was less than that in the control group. There was a significant difference between painters and the control group (p < 0.01) for RI. We believe that determination of RI in addition to NCs and the MN will present a new approach to genotoxicity studies of a population.

Assessment of cadmium genotoxicity in peripheral blood and bone marrow tissues of male Wistar rats.

In this study, Cadmium (Cd) genotoxicity was investigated in both bone marrow and peripheral blood treatment using rat micronucleus technique as genotoxicity test at acute and chronic treatment in the same animals. This study evaluated the frequency of micronuclei in the peripheral blood and bone marrow of male rats treated with unique cadmium dose (15 mg/kg. body w/day) by gavage for 60 days and acute treatment for 24 h, respectively. Mitomycin C (MMC) 2 mg/kg body wt was used as a positive control. This study shows that cadmium chloride treatment significantly induced the frequency of micronucleus in polychromatic erythrocytes in both tibia bone marrow and peripheral blood (p < 0.001, p < 0.01, respectively). This increase in micronucleus frequency shows that cadmium has a genotoxic effect on bone marrow and peripheral blood at this level. Also, in order to determine cytotoxicity in bone marrow and peripheral blood, the ratio of polychromatic erythrocytes to normochromatic erythrocytes was calculated in bone marrow and peripheral blood. Cd treatment decreased this ratio in only bone marrow. The results of this study demonstrate that Cd has both toxic and genotoxic potential in bone marrow and only genotoxic potential in peripheral blood. There is a significant difference between the control group and exposed group, including acute and chronic treatment for blood Cd level (p < 0.001). No significant difference was found between acute and chronic exposure group (p > 0.05).

Genotoxicity of thimerosal in cultured human lymphocytes with and without metabolic activation sister chromatid exchange analysis proliferation index and mitotic index.

Thimerosal is an antiseptic containing 49.5% of ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. In this study, we evaluated the genotoxic effect of thimerosal in cultured human peripheral blood lymphocytes using sister chromatid exchange analysis in culture conditions with and without S9 metabolic activation. This study is the first report investigating the genotoxic effects of thimerosal in cultured human peripheral blood lymphocyte cells using sister chromatid exchange analysis. An analysis of variance test (ANOVA) was performed to evaluate the results. Significant induction of sister chromatid exchanges was seen at concentrations between 0.2 and 0.6 microg/ml of thimerosal compared with negative control. A significant decrease (p<0.001) in mitotic index (MI) and proliferation index (PRI) as well as an increase in SCE frequency (p<0.001) was observed compared with control cultures. Our results indicate the genotoxic and cytotoxic effect of TH in cultured human peripheral blood lymphocytes at tested doses in cultures with/without S9 fraction.