Exposure to tungsten induces DNA damage and apoptosis in developing B lymphocytes

Guilbert, Cynthia; Kelly, Alexander; Petruccelli, Luca A.; Lemaire, Maryse; Mann, Koren K.

doi:10.1038/leu.2011.160

Cited by 31 publications

(24 citation statements)

References 13 publications

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“…In a recent Comet assay study, primary murine bone marrow cell cultures were treated with vehicle control or varying concentrations of ST (5–500 μg/mL) for 6 h. In all cells tested, WO 4 2− induced a significant increase in the Comet tail moment, indicating an increase in DNA breakage, and confirmed with Western blotting experiments using antibodies against γH2AX, a phosphorylated histone variant that is induced upon DNA damage ( Guilbert et al 2011 ).…”

Section: Toxicological Studiesmentioning

confidence: 73%

“…To determine whether in vivo exposure to tungsten might induce DNA damage within the bone marrow compartment, Guilbert et al (2011) exposed mice to ST in the drinking water (15 or 200 mg/mL, estimated to be 4 and 50 mg/kg/d, respectively) for 8 weeks. While WO 4 2− did not significantly alter the total bone marrow cellularity at these concentrations, it was found that WO 4 2− exposure resulted in an increase in DNA damage, as assessed by the Comet assay.…”

Section: Toxicological Studiesmentioning

confidence: 99%

“…These negative results support a lack of genotoxic potential of water-soluble and sparingly soluble tungsten substances. However, there are equivocal in vitro Comet assay results that were conducted on different cells (human peripheral lymphocytes versus mouse bone marrow cells), and equivocal in vivo micronucleus ( CCR 1989a , Covance Laboratories, Inc., 2004b , NTP 2014a ) and Comet assay ( Guilbert et al 2011 ) studies in bone marrow cells of mice that were orally exposed to water-soluble tungsten substances. Therefore, due to the equivocal in vivo results, the genotoxicity of soluble substances in bone marrow cells merits further investigation before the genotoxic potential of soluble tungsten forms can be established.…”

Section: Toxicological Studiesmentioning

confidence: 99%

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An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

Lemus¹,

Venezia

2015

Critical Reviews in Toxicology

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Tungsten is a relatively rare metal with numerous applications, most notably in machine tools, catalysts, and superalloys. In 2003, tungsten was nominated for study under the National Toxicology Program, and in 2011, it was nominated for human health assessment under the US Environmental Protection Agency's (EPA) Integrated Risk Information System. In 2005, the Agency for Toxic Substances and Disease Registry (ATSDR) issued a toxicological profile for tungsten, identifying several data gaps in the hazard assessment of tungsten. By filling the data gaps identified by the ATSDR, this review serves as an update to the toxicological profile for tungsten and tungsten substances. A PubMed literature search was conducted to identify reports published during the period 2004–2014, in order to gather relevant information related to tungsten toxicity. Additional information was also obtained directly from unpublished studies from within the tungsten industry. A systematic approach to evaluate the quality of data was conducted according to published criteria. This comprehensive review has gathered new toxicokinetic information and summarizes the details of acute and repeated-exposure studies that include reproductive, developmental, neurotoxicological, and immunotoxicological endpoints. Such new evidence involves several relevant studies that must be considered when regulators estimate and propose a tungsten reference or concentration dose.

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Section: Toxicological Studiesmentioning

confidence: 73%

Section: Toxicological Studiesmentioning

confidence: 99%

Section: Toxicological Studiesmentioning

confidence: 99%

See 1 more Smart Citation

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

Lemus¹,

Venezia

2015

Critical Reviews in Toxicology

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“…Disruption of redox processes leads to altered expression of FasL and Bcl2 in T-cells (Yang et al, 2013), and inhibition of CD8 + T-cell proliferation and function (Sklavos et al, 2008). Tungstate exposure has been associated with increased apoptosis in vitro in human and murine leukocytes (Osterburg et al, 2010; Guilbert et al, 2011); with DNA damage in vivo in bone marrow cells in C57BL/6J mice (Guilbert et al, 2011); with activation of antioxidant enzymes (Nakhaee et al, 2010; Donmez et al, 2014); and with up-regulation of pro-apoptotic genes (Lombaert et al, 2008; Harris et al, 2015) and proteins (Zhao et al, 2013) in rats and human and rodent cultured cells. However, in the present study, no increases in apoptosis, tingible body macrophages, or cell loss were evident in groups administered STD compared to control groups when hosts were evaluated using enhanced histopathology or spleen cell immunophenotyping.…”

Section: Discussionmentioning

confidence: 99%

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Frawley

Smith

White

et al. 2016

Journal of Immunotoxicology

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Tungsten is a naturally occurring, high tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0–2000 mg STD/L in their drinking water for 28 days, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3+ T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely effect cell-mediated immunity.

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“…However, the premise for the success of this cancer coadjuvants is that they differentiate between normal and transformed cells, which has not been determined for Na 2 WO 4 and is not expected to be the case due to its nonspecific mechanisms of action. Furthermore, on the one hand, Na 2 WO 4 itself has been reported to induce DNA damage (Guilbert et al, 2011;Kelly et al, 2013) and, on the other, longlasting cell cycle arrest induced by Na 2 WO 4 would favor chronic senescence and cell deterioration, impacting on tissue function and tumorigenesis (Canaud & Bonventre, 2015;Marongiu et al, 2017;Sturmlechner, Durik, Sieben, Baker, & van Deursen, 2017).…”

Section: Na 2 Wo 4 and Cancermentioning

confidence: 99%

Sodium tungstate: Is it a safe option for a chronic disease setting, such as diabetes?

Bertinat

Westermeier

Gatica

et al. 2018

Journal Cellular Physiology

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Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by pancreatic β cells, the resistance of peripheral tissues to the action of the hormone, or both, and is characterized by chronic hyperglycemia leading to organ damage and failure. Tight glycemic control represents the best therapy to delay or stop progression of diabetes, with many antidiabetic drugs being commercially available nowadays. However, no ideal normoglycemic agent has been developed as yet, and those already available still induce hypoglycemia and/or weight gain as major side effects, worsening glycemic control. In this respect, the inorganic salt sodium tungstate (Na WO ) has been proven to offer a good antidiabetic alternative in different animal models of diabetes, reducing body weight and normalizing glycemia without causing hypoglycemic episodes. The mechanisms of action mediating the potent antidiabetic actions but also the spectrum of undesirable effects of Na WO are still poorly understood. In fact, along with its beneficial effects, Na WO has been consistently reported to be toxic and even carcinogenic. Given that Na WO is accumulated in the kidneys for elimination, here, we discuss a possible association between long-term Na WO treatment and a higher risk of renal carcinogenesis in diabetic individuals.

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Exposure to tungsten induces DNA damage and apoptosis in developing B lymphocytes

Cited by 31 publications

References 13 publications

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Sodium tungstate: Is it a safe option for a chronic disease setting, such as diabetes?

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Exposure to tungsten induces DNA damage and apoptosis in developing B lymphocytes

Cited by 31 publications

References 13 publications

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water

Sodium tungstate: Is it a safe option for a chronic disease setting, such as diabetes?

Contact Info

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Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water