Juan José Rodríguez-Mercado

Genotoxic effects of vanadium(IV) in human peripheral blood cells

Vanadium has been considered an aneuploidogen; however, there is controversial information about the clastogenic effects of vanadium compounds. In this study, the genotoxicity of vanadium(IV) tetraoxide (V(2)O(4)) was evaluated in human cultured lymphocytes and leukocytes using the mitotic index (MI), the replicative index (RI), chromosome aberrations (CA), sister chromatid exchanges (SCE), satellite associations (SA) and the single cell gel electrophoresis (SCGE) assay. This chemical induced a clear dose-response in MI inhibitions and modifications in the RI. In the CA, including breaks and exchanges and in the SCE, a significant increase appeared in the treated group compared with the controls. The SA test did not reveal an important difference. For the detection of genotoxic properties of vanadium(IV) using the SCGE assay, the 2 h evaluation period was not long enough for the chemical to enter the cell. These results indicate that vanadium(IV) tetraoxide is capable of inducing cytotoxic and cytostatic effects and chromosomal damage.

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 (Tl3+), 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.

DNA damage induction in human cells exposed to vanadium oxides in vitro

Vanadium and vanadium salts cause genotoxicity and elicit variable biological effects depending on several factors. In the present study, we analyzed and compared the DNA damage and repair processes induced by vanadium in three oxidation states. We used human blood leukocytes in vitro and in a single cell gel electrophoresis assay at two pH values. We observed that vanadium(III) trioxide and vanadium(V) pentoxide produced DNA single-strand breaks at all of the concentrations (1, 2, 4, or 8 μg/ml) and treatment times (2, 4, or 6 h) tested. Vanadium(IV) tetraoxide treatment significantly increased DNA damage at all concentrations for 4 or 6 h of treatment but not for 2 h of treatment. The DNA repair kinetics indicated that most of the cells exposed to vanadium III and V for 4 h recovered within the repair incubation time of 90 min; however, those exposed to vanadium(IV) repaired their DNA within 120 min. The data at pH 9 indicated that vanadium(IV) tetraoxide induced DNA double-strand breaks. Our results show that the genotoxic effect of vanadium can be produced by any of its three oxidation states. However, vanadium(IV) induces double-strand breaks, and it is known that these lesions are linked with forming structural chromosomal aberrations.

Chromosomal damage induced by vanadium oxides in human peripheral lymphocytes.

Fly ash, the inorganic residue resulting from the combustion of some fuels, may almost exclusively contain vanadium oxides, compounds which exert potential toxic effects on a wide variety of in vitro and in vivo biological systems. Because information related to the oxidation state responsible for inducing genotoxic effects is controversial, the aim of the present study was to evaluate the effects of three vanadium salts in vitro. Human peripheral lymphocyte cultures were exposed to 1, 2, 4, or 8 μg/mL of vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V2O3, V2O4, or V2O5, respectively). These cultures were then screened for structural chromosomal aberrations, and mitotic index (MI) measurements were made. Cytogenetic evaluations showed that only V2O4 increased the percentage of aberrant cells (without gaps) and chromosome damage (including and excluding gaps), while all compounds led to a decrease in the MI. These results demonstrate that vanadium(III), vanadium(IV), and vanadium(V) are all capable of inducing cytotoxicity, but only oxidation state IV induces clastogenic effects.

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.

Genotoxicity assessment of human peripheral Lymphocytes induced by thallium(I) and thallium(III)

ABSTRACT Thallium is a non-essential metal with a wide range of industrial uses. However, thallium is also a potential pollutant with high potential toxicity to humans. In the present study, we analyzed and compared the cellular and genotoxic effects of thallium in two main oxidation states by applying chromosome aberration assays to human peripheral lymphocytes. We observed that thallium(I) sulfate reduced the mitotic index at all tested concentrations (0.5, 1, 5, 50 and 100 μg/mL), whereas thallium(III) chloride was toxic at concentrations ≥1 μg/mL. Thallium(I) and thallium(III) treatment significantly increased structural chromosomal aberrations, with and without gaps, and increased the percentage of aberrant cells without gaps. Furthermore, satellite associations and numerical chromosomal aberration tests showed significant differences at a few of the tested concentrations. The satellite association test is related to aneuploidy. Thallium salts increased satellite associations when hyperploid cells were observed. Our results indicated that the two oxidation states of thallium induced toxicity in vitro – i.e. cyto/genotoxic (clastogenic and aneuploidogenic) effects.

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

Abstract 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.

Genotoxicity of Casiopeina III-Ea in mouse bone marrow cells

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

Abstract 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.