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

Abstract

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.

The Role of Vitamin C in the Protection and Modulation of Genotoxic Damage Induced by Metals Associated with Oxidative Stress

“…In a previous study, we observed that the frequency of micronuclei in polychromatic erythrocytes (MN-PCE) increased with the administration of 40 mg/kg of V 2 O 5 through ip [8], consistent with other studies testing soluble vanadium compounds (Na 3 VO 4 , SVO 5, and NH 4 VO 3 ) [34][35][36]. However, the in vivo administration of vitamin C prior to the V 2 O 5 injection decreased MN-PCE formation compared to administering V 2 O 5 alone, reducing basal MN-PCE, and presenting the strongest protection against genotoxic damage induced by V 2 O 5 .…”

Evaluation of cII mutations in lung of male Big Blue mice exposed by inhalation to vanadium pentoxide for up to 8 weeks

“…However, recent studies reported a slight increase in 8-oxodGuo DNA lesions in lungs of female B 6 C 3 F 1 mice exposed to 1 or 4 mg/m 3 V 2 O 5 for 16 days by nose-only inhalation [21], and increased micronuclei in peripheral blood in male but not female CD1 mice exposed to 1.4 mg/m 3 V 2 O 5 for 2 h per week for 4 weeks by aerosol inhalation [20]. 8-oxodGuo DNA lesions are likely to be mutagenic, and impaired or defective repair of these lesions can induce mostly G → T and A → C transversions [22,27], which can be detected in lungs of BB mice following exposure to V 2 O 5 .…”

“…In CD1 mice, intraperitoneal administration of V 2 O 5 induced significant DNA damage in multiple tissues, such as lung, heart, liver, bone marrow, spleen, and kidney, as measured by the alkaline comet assay 24 h following the treatment, but the increase was not concentration-dependent [19]. Recently, the same authors exposed male and female CD1 mice to 1.4 mg/m 3 V 2 O 5 for 2 h per week for 4 weeks by aerosol inhalation and reported a significant induction of micronucleus frequency in the peripheral blood only in males [20]. Although toxic exposure levels were reached in both males and females, as evidenced by the significant decrease in reticulocytes seen in both sexes, the absence of genotoxic effects in the female mice was attributed to the protective effect against oxidative stress conferred by their higher estrogen levels.…”

Oxidative Stress and Vanadium

“…Information related to the carcinogenic and genotoxic potential of vanadium pentoxide (V 2 O 5 ) is limited [14]. In both animal and human models, the effects on the DNA caused by vanadium include single strand breaks, micronuclei, chromosomal aberrations (structural and numerical), and oxidation of nitrogenous bases [15,16]. The spectrum of alterations that DNA might have as a consequence of free radicals interaction, in this case caused by vanadium, are: deoxyribose oxidation, modification of nitrogen bases, chain cross-linking, and ruptures [6].…”