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.

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.

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.

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.

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 microg/mL of vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V(2)O(3), V(2)O(4), or V(2)O(5), respectively). These cultures were then screened for structural chromosomal aberrations, and mitotic index (MI) measurements were made. Cytogenetic evaluations showed that only V(2)O(4) 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.