Cytogenetic damage by vanadium(IV) and vanadium(III) on the bone marrow of mice.

Vanadium is a strategic metal that has many important industrial applications and is generated by the use of burning fossil fuels, which inevitably leads to their release into the environment, mainly in the form of oxides. The wastes generated by their use represent a major health hazard. Furthermore, it has attracted attention because several genotoxicity studies have shown that some vanadium compounds can affect DNA; among the most studied compounds is vanadium pentoxide, but studies in vivo with oxidation states IV and III are scarce and controversial. In this study, the genotoxic and cytotoxic potential of vanadium oxides was investigated in mouse bone marrow cells using structural chromosomal aberration (SCA) and mitotic index (MI) test systems. Three groups were administered vanadium(IV) tetraoxide (V2O4) intraperitoneally at 4.7, 9.4 or 18.8 mg/kg, and three groups were administered vanadium(III) trioxide (V2O3) at 4.22, 8.46 or 16.93 mg/kg body weight. The control group was treated with sterile water, and the positive control group was treated with cadmium(II) chloride (CdCl2). After 24 h, all doses of vanadium compounds increased the percentage of cells with SCA and decreased the MI. Our results demonstrated that under the present experimental conditions and doses, treatment with V2O4 and V2O3 induces chromosomal aberrations and alters cell division in the bone marrow of mice.

Evaluation of Clastogenic/Aneugenic Damage Using the FISH Micronucleus Assay in Mice Exposed to Chromium (VI).

BACKGROUND/AIM: Exposure to chromium (VI) [Cr(VI)] has been postulated to be associated with the induction of cancer. In vivo studies utilizing biomarkers of genotoxic damage could aid in elucidating the mechanisms underlying the genotoxic effects of Cr(VI) and their relationship with carcinogenesis. In this study, the origin (clastogenic and/or aneugenic damage) and kinetics of micronuclei (MN) induced by Cr(VI) were investigated. MATERIALS AND METHODS: Hsd:ICR female mice were divided into groups of five individuals each. MN kinetics were measured in groups treated with 20 or 25 mg/kg CrO3 intraperitoneally using acridine orange-coated slides in peripheral blood obtained from the caudal vein 0, 12, 24, 36, 48, 60, and 72 h after treatment. Whereas identification of MN with centromeric DNA (MNK+) was measured at the dose of 20 mg/kg of CrO3, using fluorescence in situ hybridization (FISH) with a centromere-specific probe in peripheral blood obtained at 0, 12, and 48 h after treatment. Control groups were administered vehicle only. RESULTS: Total MN were quantified and the clastogenic/aneugenic effects of Cr(VI) were evaluated based on the proportion of MNK+ versus micronuclei without centromeric DNA (MNK-). There was a significant increase in MN frequencies beginning at 12 h in the Cr(VI)-treated groups demonstrating its genotoxicity. When calculating the MNK+ as a percentage of the total MN, the increase was significant beginning 12 h after treatment. CONCLUSION: The fact that the MNK+ and MNK- were observed at both evaluation times corroborates Cr(VI) as a genotoxic agent and demonstrates that both clastogenic and aneugenic damages are involved in the formation of MN.

Vanadium(IV) oxide affects embryonic development in mice.

Vanadium(V) and vanadium(IV) are the predominant redox forms present in the environment, and epidemiological studies have reported that prenatal vanadium exposure is associated with restricted fetal growth and adverse birth outcomes. However, data about the toxic effects of vanadium(IV) oxide (V2 O4 ) on the development of mammals are still limited. Therefore, in this work, 4.7, 9.4, or 18.7 mg/kg body weight/injection/day V2 O4 was administered through an intraperitoneal (ip) injection to pregnant mice from gestational days 6 to 16. The results showed that V2 O4 produced maternal and embryo-fetal toxicity and external abnormalities in the offspring, such as malrotated and malpositioned hind limbs, hematomas and head injuries. Moreover, the skeletons of the fetuses presented reduced ossification of the cranial bones, including the frontal and parietal bones, corresponding to head injuries observed in the external assessment of the fetuses. These results demonstrate that administration of V2 O4 to pregnant females in the organogenesis period adversely affects embryonic development.

Vanadium oxides modify the expression levels of the p21, p53, and Cdc25C proteins in human lymphocytes treated in vitro.

In vitro assays have demonstrated that vanadium compounds interact with biological molecules similar to protein kinases and phosphatases and have also shown that vanadium oxides decrease the proliferation of cells, including human lymphocytes; however, the mechanism, the phase in which the cell cycle is delayed and the proteins involved in this process are unknown. Therefore, we evaluated the effects of vanadium oxides (V2 O3 , V2 O4 and V2 O5 ) in human lymphocyte cultures (concentrations of 2, 4, 8, or 16 µg/ml) on cellular proliferation and the levels of the p53, p21 and Cdc25C proteins. After 24 h of treatment with the different concentrations of vanadium oxides, the cell cycle phases were determined by evaluating the DNA content using flow cytometry, and the levels of the p21, p53 and Cdc25C proteins were assessed by Western blot analysis. The results revealed that the DNA content remained unchanged in every phase of the cell cycle; however, only at high concentrations did protein levels increase. Although, according to previous reports, vanadium oxides induce a delay in proliferation, DNA analysis did not show this occurring in a specific cell cycle phase. Nevertheless, the increases in p53 protein levels may cause this delay.

Antigenotoxic effects of (-)-epigallocatechin-3-gallate (EGCG) and its relationship with the endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct repair (8-OHdG), and apoptosis in mice exposed to chromium(VI).

This study aimed to investigate the relationship between endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct (8-OHdG) repair, and apoptosis in mice treated with chromium(VI) alone and in the presence of the antigenotoxic compound (-)-epigallocatechin-3-gallate (EGCG). Groups of 5 Hsd:ICR male mice were divided and treated as follows: (1) control, vehicle only; (2) EGCG, 8.5 mg/kg by gavage alone; (3) CrO3, 20 mg/kg intraperitoneally alone; and (4) EGCG combined with CrO3, EGCG was administered 4 hr prior to CrO3. Peripheral blood parameters were analyzed before treatment administration (time 0), and 48 hr after exposure. The administration of EGCG increased 8-OHdG levels and superoxide dismutase (SOD) activity. Treatment with CrO3 increased number of micronucleus (MN) presence, elevated apoptotic/necrotic cells frequencies, decreased 8-OHdG levels, diminished total antioxidant capacity (TAC), increased glutathione (GSH) total levels, and lowered SOD activity. Administration of EGCG prior to treatment with CrO3 resulted in lower concentrations of MN, reduced apoptotic and necrotic cell number, and restored TAC and SOD activity to control levels. It is conceivable that the dose of EGCG plays an important role in the genotoxic damage protection pathways. Thus, this study confirms the action of EGCG as an antigenotoxic agent against chromium(VI)-induced oxidative insults and demonstrates potential protective pathways for EGCG actions to counteract genotoxic damage induced by this metal.

Effect on the offspring of pregnant females CD-1 mice treated with a single thallium(I) application.

Thallium (Tl) is a highly toxic metal for human beings; higher amounts found in diverse fluids of pregnant women are associated with low birth weight and preterm birth. However, experimental data concerning their effects on the embryonic development of mammalian organisms are limited. Hence, in the present work, TI(I) acetate of 0, 4.6, 9.2, or 18.5 mg/kg body weight were administered by intraperitoneal injection to groups of 10 pregnant CD-1 mice on the 7th gestational day, and animals were sacrificed on day 18 of gestation. The fetuses obtained showed some variations, such as trunk bent over (18.5 mg/kg), tail variations (all doses), forelimbs malrotation and hind limbs (all doses). Skeletal examination of the fetuses showed a delay in the ossification of skull bones, ribs, and limbs (all doses). In conclusion, the Intraperitoneal injection of Tl(I) acetate to pregnant mice induced morphological variations and a delay of the fetus ossification.

Premature chromatid separation and altered proliferation of human leukocytes treated with vanadium (III) oxide.

Vanadium is a widely distributed metal in the Earth's surface and is released into the environment by either natural or anthropogenic causes. Vanadium (III) oxide (V2O3) is present in the environment, and many organisms are exposed to this compound; however, its effects at the cellular and genetic levels are still unknown. Therefore, in this study, the ability of V2O3 to induce chromosomal damage and impair cell proliferation was tested on human leukocytes in vitro. The cultures cells were treated for 48 h with different concentrations 2, 4, 8 or 16 µg/mL of V2O3, and we use the sister chromatid exchange's (SCE) test and the viability assay to evaluate the effects. In the results, no change was observed in either the viability or the frequency of SCE; however, a significant increase was observed in the incidence of premature chromatid separation (PCS), and a decrease was observed in both the mitotic index (MI) and the replication index (RI). Therefore, it can be suggested that V2O3 induces a genotoxic effect at the centromere level, indicating that it is a cause of aneuploidy that is capable of altering cell cycle progression.

In vitro DNA damage by Casiopeina II-gly in human blood cells.

A variety of metal ions have biological functions, and many researchers have not actively investigated copper compounds, based on the assumption that endogenous metals might be less toxic. In the present study, we used a dual fluorochrome method and a single cell gel electrophoresis (SCGE) assay at pH > 13 to evaluate the cell viability and DNA damage induced by a copper-based antineoplastic drug, Casiopeina II-gly®, at concentrations of 1.04, 2.08, 4.17, 8.35 or 16 µg/mL in human peripheral-blood leukocytes in vitro. We observed that Casiopeina II-gly® reduced cell viability at high concentrations (8.35 and 16 µg/mL) and induced DNA damage characterized by single-strand breaks and alkali labile sites at several concentrations from 2.08 to 16 µg/mL. This chemical clearly affected DNA migration in a concentration- and time-dependent manner and induced genotoxic effects in few minutes (>20 min), at which point the genotoxicity was followed by cytotoxicity.

Genotoxicity of Casiopeina III-Ea in mouse bone marrow cells.

Casiopeina III-Ea® (Cas III-Ea®) is a chelated copper complex with antineoplastic activity that is capable of reducing tumor size and inducing antiproliferative and apoptotic effects. However, little is known about its in vivo genotoxic effects. Therefore, this study evaluated two cytogenetic and two proliferative parameters 24 h after the administration of Casiopeina III-Ea® to male CD-1 mice. Three doses of Cas III-Ea® were administered by intraperitoneal injections of 1.69, 3.39 and 6.76 mg/kg (corresponding to 1/8, 1/4 and 1/2 of LD50, respectively). A reduction in the mitotic index (MI) and an increased numbers of cells with structural chromosomal aberrations (SCA) were detected. Additionally, a low but significant increase in the frequency of sister chromatid exchange (SCE) was observed at the highest dose. Changes in the DNA replication index (RI) were not observed. These results indicate that Casiopeina III-Ea® shows cytotoxic and clastogenic activity in bone marrow cells from treated mice.

In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice.

This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5.

Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.

This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.

[IN VIVO EFFECT OF RED WINE UNDILUTED, DILUTED (75%) AND ALCOHOL-FREE ON THE GENOTOXIC DAMAGE INDUCED BY POTENTIAL CARCINOGENIC METALS: CHROMIUM [VI]]. / EFECTO IN VIVO DEL VINO TINTO SIN DILUIR, DILUIDO (75%) Y SIN ALCOHOL SOBRE EL DAÑO GENOTÓXICO INDUCIDO POR METALES PESADOS CON POTENCIAL CANCERÍGENO: CROMO [VI].

INTRODUCTION: the carcinogenesis may be initiated and promoted by the oxidative DNA damage. The compounds of chrome (Cr [VI]) cause oxidative stress (EOx) and are recognized as carcinogens in humans. In this sense, it is proposed that drinks with a high antioxidative potential, such as red wine, may have protective or modulatory effects on the oxidative DNA damage. OBJECTIVE: to study the effects of the administration in vivo of undiluted, diluted (75%) and alcohol-free red wine on the genotoxic damage induced by carcinogenic metals (Cr [VI]), by evaluating the micronucleus (MN) in polychromatic erythrocytes (EPC) in mice (CD-1). MATERIAL AND METHOD: it was randomly organized the follow groups: (i) control, (ii) undiluted, diluted and alcohol-free red wine (free access), (iii) CrO3 (20 mg/kg by intraperitoneal route) and (iv) CrO3-red wine. The evaluations were made in blood samples obtained from the caudal vein, in which it was identified the MN and EPC before, during and after treatments. RESULTS AND DISCUSSION: the red wine (diluted and alcohol-free) was capable of decreasing the averages of MN induced by CrO3, demonstrating its modular capacity in vivo in the oxidative DNA damage caused by EOx-induced carcinogens. The administration of only undiluted red wine presented toxic effects. CONCLUSIONS: our results raises expectations on the use of substances like the red wine for the protection or modulation of genotoxic damage, encouraging its application in the carcinogenic and mutagenic processes.

Introducción: la carcinogénesis puede ser iniciada y promovida por el daño oxidativo al ADN. Los compuestos de cromo (Cr) [VI] generan estrés oxidativo (EOx) y son reconocidos como cancerígenos en humanos. En este sentido, se plantea que bebidas que presentan un alto potencial antioxidante, como el vino tinto, pudieran tener efectos protectores o moduladores del daño oxidativo al ADN. Objetivo: estudiar los efectos de la administración in vivo de vino tinto sin diluir, diluido (75%) y sin alcohol, sobre el daño genotóxico inducido por metales cancerígenos (Cr [VI]), mediante la evaluación de micronúcleos (MN) en eritrocitos policromáticos (EPC) de ratones (CD-1). Material y método: se conformaron aleatoriamente los siguientes grupos: (i) testigo, (ii) vino tinto sin diluir, diluido o sin alcohol (libre acceso), (iii) CrO3 (20 mg/kg por vía intraperitoneal) y (iv) vino tinto-CrO3. Las evaluaciones se realizaron en muestras de sangre obtenidas de la vena caudal, en las que se identificaron los MN en EPC antes, durante y después de los tratamientos. Resultados y discusión: el vino tinto (diluido y sin alcohol) fue capaz de disminuir los promedios de MN inducidos por el CrO3, lo que muestra su capacidad para modular in vivo el daño oxidativo al ADN causado por cancerígenos inductores de EOx. La administración únicamente de vino tinto sin diluir presentó efectos tóxicos. Conclusiones: nuestros resultados generan expectativas sobre el empleo de sustancias como el vino tinto en la protección o modulación del daño genotóxico, lo que podría conducir a su aplicación en los procesos de carcinogénesis y mutagénesis.

Efecto in vivo del vino tinto sin diluir, diluido (75%) y sin alcohol sobre el daño genotóxico inducido por metales pesados con potencial cancerígeno: cromo [VI] / In vivo effect of red wine undiluted, diluted (75%) and alcohol-free on the genotoxic damage induced by potential carcinogenic metals: chromium [VI]

Introducción: la carcinogénesis puede ser iniciada y promovida por el daño oxidativo al ADN. Los compuestos de cromo (Cr) [VI] generan estrés oxidativo (EOx) y son reconocidos como cancerígenos en humanos. En este sentido, se plantea que bebidas que presentan un alto potencial antioxidante, como el vino tinto, pudieran tener efectos protectores o moduladores del daño oxidativo al ADN. Objetivo: estudiar los efectos de la administración in vivo de vino tinto sin diluir, diluido (75%) y sin alcohol, sobre el daño genotóxico inducido por metales cancerígenos (Cr [VI]), mediante la evaluación de micronúcleos (MN) en eritrocitos policromáticos (EPC) de ratones (CD-1). Material y método: se conformaron aleatoriamente los siguientes grupos: (i) testigo, (ii) vino tinto sin diluir, diluido o sin alcohol (libre acceso), (iii) CrO3 (20 mg/kg por vía intraperitoneal) y (iv) vino tinto-CrO3. Las evaluaciones se realizaron en muestras de sangre obtenidas de la vena caudal, en las que se identificaron los MN en EPC antes, durante y después de los tratamientos. Resultados y discusión: el vino tinto (diluido y sin alcohol) fue capaz de disminuir los promedios de MN inducidos por el CrO3, lo que muestra su capacidad para modular in vivo el daño oxidativo al ADN causado por cancerígenos inductores de EOx. La administración únicamente de vino tinto sin diluir presentó efectos tóxicos. Conclusiones: nuestros resultados generan expectativas sobre el empleo de sustancias como el vino tinto en la protección o modulación del daño genotóxico, lo que podría conducir a su aplicación en los procesos de carcinogénesis y mutagénesis (AU)

Introduction: the carcinogenesis may be initiated and promoted by the oxidative DNA damage. The compounds of chrome (Cr [VI]) cause oxidative stress (EOx) and are recognized as carcinogens in humans. In this sense, it is proposed that drinks with a high antioxidative potential, such as red wine, may have protective or modulatory effects on the oxidative DNA damage. Objective: to study the effects of the administration in vivo of undiluted, diluted (75%) and alcohol-free red wine on the genotoxic damage induced by carcinogenic metals (Cr [VI]), by evaluating the micronucleus (MN) in polychromatic erythrocytes (EPC) in mice (CD-1). Material and method: it was randomly organized the follow groups: (i) control, (ii) undiluted, diluted and alcohol-free red wine (free access), (iii) CrO3 (20 mg/kg by intraperitoneal route) and (iv) CrO3 -red wine. The evaluations were made in blood samples obtained from the caudal vein, in which it was identified the MN and EPC before, during and after treatments. Results and discussion: the red wine (diluted and alcohol-free) was capable of decreasing the averages of MN induced by CrO3, demonstrating its modular capacity in vivo in the oxidative DNA damage caused by EOx-induced carcinogens. The administration of only undiluted red wine presented toxic effects. Conclusions: our results raises expectations on the use of substances like the red wine for the protection or modulation of genotoxic damage, encouraging its application in the carcinogenic and mutagenic processes (AU)

Hydroxyurea induces chromosomal damage in G2 and enhances the clastogenic effect of mitomycin C in Fanconi anemia cells.

Fanconi's anemia (FA) is a recessive disease; 16 genes are currently recognized in FA. FA proteins participate in the FA/BRCA pathway that plays a crucial role in the repair of DNA damage induced by crosslinking compounds. Hydroxyurea (HU) is an agent that induces replicative stress by inhibiting ribonucleotide reductase (RNR), which synthesizes deoxyribonucleotide triphosphates (dNTPs) necessary for DNA replication and repair. HU is known to activate the FA pathway; however, its clastogenic effects are not well characterized. We have investigated the effects of HU treatment alone or in sequential combination with mitomycin-C (MMC) on FA patient-derived lymphoblastoid cell lines from groups FA-A, B, C, D1/BRCA2, and E and on lymphocytes from two unclassified FA patients. All FA cells showed a significant increase (P < 0.05) in chromosomal aberrations following treatment with HU during the last 3 h before mitosis. Furthermore, when FA cells previously exposed to MMC were treated with HU, we observed an increase of MMC-induced DNA damage that was characterized by high occurrence of DNA breaks and a reduction in rejoined chromosomal aberrations. These findings show that exposure to HU during G2 induces chromosomal aberrations by a mechanism that is independent of its well-known role in replication fork stalling during S-phase and that HU interfered mainly with the rejoining process of DNA damage. We suggest that impaired oxidative stress response, lack of an adequate amount of dNTPs for DNA repair due to RNR inhibition, and interference with cell cycle control checkpoints underlie the clastogenic activity of HU in FA cells. Environ. Mol. Mutagen. 56:457-467, 2015. © 2015 Wiley Periodicals, Inc.

Evaluation of cytogenetic and DNA damage caused by thallium(I) acetate in human blood cells.

Although thallium is detrimental to all living organisms, information regarding the mutagenic and genotoxic effects of this element and its compounds remains scarce. Therefore, we tested the genotoxic and cytotoxic effects of thallium(I) acetate on human peripheral blood cells in vitro using structural chromosomal aberrations (SCAs), sister chromatid exchanges (SCEs), and single-cell gel electrophoresis (at pH >13 or 12.1) analysis. Whole blood samples were incubated with 0.5, 1, 5, 10, 50, or 100 µg/mL thallium salt. Exposure to this metal compound resulted in a clear dose-dependent reduction in the mitotic and replicative indices. An increase in SCAs was evident in the treated group compared with the control group, and significant differences were observed in the percentage of cells with SCAs when metaphase cells were treated with 0.5-10 µg/mL of thallium(I). The SCE test did not reveal any significant differences. We observed that a 1-h treatment with thallium(I) at pH > 13 significantly increased the comet length for all the concentrations tested; however, at pH 12.1, only the two highest concentrations affected the comet length. These results suggested that thallium(I) acetate induces cytotoxic, cytostatic, and clastogenic effects, as well as DNA damage.

Antigenotoxic effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on chromium trioxide-induced micronuclei in the polychromatic erythrocytes of mouse peripheral blood.

This study was conducted to investigate the modulating effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on the genotoxic damage induced by Cr(VI) in polychromatic erythrocytes of CD-1 mice. The animals were divided into the following groups: (i) vehicle only; (ii) flavonoids (10 mg/kg EGCG, 100 mg/kg quercetin, 625 mg/kg rutin, or 100-625 mg/kg quercetin-rutin); (iii) Cr(VI) (20 mg/kg of CrO3); and (iv) flavonoids concomitantly with Cr(VI). All of the treatments were administered intraperitoneally (i.p.). The genotoxic damage was evaluated based on the number of micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein 0, 24, 48, and 72 h after treatment. Groups treated with EGCG and quercetin exhibited no significant statistical changes in induction of MN-PCE. However, CrO3 treatment significantly increased MN-PCE induction 24 and 48 h after injection. Treatment with flavonoids prior to CrO3 exposure decreased MN-PCE induction compared with CrO3 only. The magnitudes of the potency of flavonoids were in the following order: rutin (82%) > quercetin (64%) > quercetin-rutin (59%) and EGCG (44%). The group treated with rutin significantly reduced genotoxic damage in mice treated with Cr(VI) (antioxidant effect). However rutin exerted a marginal genotoxic effect when administered alone (pro-oxidant effect). Our findings suggest protective effects of EGCG, quercetin, and rutin against genotoxic damage induced by Cr(VI).

Sex differences in blood genotoxic and cytotoxic effects as a consequence of vanadium inhalation: micronucleus assay evaluation.

Vanadium is an environmental pollutant attached to the smallest air suspended particles that enters into the respiratory tract reaching the systemic circulation. The oxidative state of this element and sex are factors related to its toxicity. In this study, we explored sex-associated genotoxic and cytotoxic differences in a mouse experimental model. Mice inhaled V2O5 (0.02 M) 2 h/twice a week; blood samples were obtained at 24 h and every week until the end of the 4-week exposure. Samples were processed for fluorochrome-mediated viability and a micronucleus assay in slides pre-covered with acridine orange (AO). The results showed that males were more susceptible to genotoxicity during the exposure in contrast to the females. In peripheral blood leukocytes, no cytotoxic differences were observed in both, females or males, but the decrease in circulating reticulocytes provides evidence of the metal's cytotoxic effect on the bone marrow (BM). A significant decrease in reticulocytes was observed during the experiment independent of the animal's sex. The present findings might be explained by the interaction of the metal with the enzymes that control erythropoiesis or a direct effect on erythropoietin production might explain our findings; however, an absence of the genotoxic effects in females could be a consequence of the protective effect against oxidative stress by their higher estrogen levels. This study contributes to a better understanding of the mechanisms by which vanadium induces adverse effects in biological systems.

Antigenotoxic and apoptotic activity of green tea polyphenol extracts on hexavalent chromium-induced DNA damage in peripheral blood of CD-1 mice: analysis with differential acridine orange/ethidium bromide staining.

This study was conducted to investigate the modulating effects of green tea polyphenols on genotoxic damage and apoptotic activity induced by hexavalent chromium [Cr (VI)] in CD-1 mice. Animals were divided into the following groups: (i) injected with vehicle; (ii) treated with green tea polyphenols (30 mg/kg) via gavage; (iii) injected with CrO3 (20 mg/kg) intraperitoneally; (iv) treated with green tea polyphenols in addition to CrO3. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCEs) obtained from peripheral blood at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. Treatment of green tea polyphenols led to no significant changes in the MN-PCEs. However, CrO3 treatment significantly increased MN-PCEs at 24 and 48 h after injection. Green tea polyphenols treatment prior to CrO3 injection led to a decrease in MN-PCEs compared to the group treated with CrO3 only. The average of apoptotic cells was increased at 48 h after treatment compared to control mice, suggesting that apoptosis could contribute to eliminate the DNA damaged cells induced by Cr (VI). Our findings support the proposed protective effects of green tea polyphenols against the genotoxic damage induced by Cr (VI).

Genetic toxicology of thallium: a review.

This review summarizes the current knowledge about the general toxicity of thallium (Tl) and its environmental sources, with special emphasis placed on its potential mutagenic, genotoxic, and cytotoxic effects on both eukaryotic and prokaryotic cells. Tl is a nonessential heavy metal that poses environmental and occupational threats as well as therapeutic hazards because of its use in medicine. It is found in two oxidation states, thallous (Tl(+)) and thallic (Tl(3+)), both of which are considered highly toxic to human beings and domestic and wild organisms. Many Tl compounds are colorless, odorless and tasteless, and these characteristics, combined with the high toxicity of TI compounds, have led to their use as poisons. Because of its similarity to potassium ions (K(+)), plants and mammals readily absorb Tl(+) through the skin and digestive and respiratory systems. In mammals, it can cross the placental, hematoencephalic, and gonadal barriers. Inside cells, Tl can accumulate and interfere with the metabolism of potassium and other metal cations, mimicking or inhibiting their action. The effects of Tl on genetic material have not yet been thoroughly explored, and few existing studies have focused exclusively on Tl(+). Both in vivo and in vitro studies indicate that Tl compounds can have a weak mutagenic effect, but no definitive effect on the induction of primary DNA damage or chromosomal damage has been shown. These studies have demonstrated that Tl compounds are highly toxic and lead to changes in cell-cycle progression.