Mutagenicity, carcinogenicity and teratogenicity of antimony compounds

doi:10.1016/S0165-1110(96)90003-2

Mutation Research/Reviews in Genetic Toxicology

Volume 366, Issue 1, October 1996, Pages 1-8

https://doi.org/10.1016/S0165-1110(96)90003-2 Get rights and content

Abstract

The paper reviews the information available concerning the mutagenic, teratogenic and carcinogenic effects of antimony. A claim that antimony compounds could have mutagenic properties is based on insufficient and not particularly relevant data. Additional experiments, particularly with organic antimony compounds, would be desirable, but from what we know already, one may be confident that antimony is less a mutagenic risk than many other metals such as As, Cr, Ni, among others. Evidence for a carcinogenic risk of antimony in experimental animals was judged by the IARC sufficient for antimony trioxide and limited for antimony trisulfide. In man, IARC considered antimony trioxide as possibly carcinogenic. However, exposure in all studies on which these conclusions are based also involved other proven or likely carcinogenic compounds. Studies with pure antimony compounds, especially those used in therapy, need to be performed to clarify the situation. Although some indications exist that antimony trioxide could interfere with embryonic and fetal development, the studies seem not entirely conclusive. It is regrettable that, at least to our knowledge, the outcome of pregnancy in women treated with antimony compounds for leishmaniasis has not been studied. In conclusion, it appears that mutagenic, carcinogenic and teratogenic risks of antimony compounds, if they exists at all, are not very important.

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Antimony (Sb) is a potentially toxic and carcinogenic cumulative contaminant that poses a serious threat to aquatic ecosystems. To better clarify the genotoxicity of Sb and its mechanism of action. In this study, we investigated DNA damage and genome-wide variation in the liver of a model organism, zebrafish (Danio rerio), under subacute Sb exposure and explored its potential toxicological mechanisms. The results showed that medium and high concentrations of Sb significantly reduced the total antioxidant capacity and increased the content of reactive oxygen species in zebrafish liver, and further studies revealed that it increased oxidative DNA damage and DNA-DNA cross-link (DDC), but had little effect on DNA-protein cross-link (DPC). The result of resequencing showed that the mutation sites of the genes with high concentrations of Sb were higher than those with medium concentrations, and the mutation was mainly a single nucleotide. The pathways significantly enriched for nonsynonymous single nucleotide polymorphisms (SNPs) and insertion/deletion mutations (InDels) variant genes in the coding regions of both the medium and high Sb-treated groups were ECM-receptor interactions, and the high Sb-treated group also included lysine degradation, hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This suggests that ECM-receptor interactions play an important role in the mechanism of antimony toxicity to the liver of zebrafish.
Potential of versatile bacteria isolated from activated sludge for the bioremediation of arsenic and antimony
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Two bacterial strains belonging to the genus Shinella were isolated from the activated sludge of a domestic wastewater treatment plant and could autotrophically oxidize As(III) to As(V) under aerobic conditions. Kinetic studies indicated that the autotrophic As(III) oxidation rate of both strains matched the Monod model well, and strain VKA3 exhibited higher kinetic parameters compared to strain VKA4 (μ_max = 124.16 μM/h and K_s = 4407.19 μM vs. μ_max = 59.00 μM/h and K_s = 1787.03 μM). The versatility of both strains was expressed through their flexible growth under heterotrophic conditions in the presence of yeast extract and anaerobic As(III) coupled with denitrification. Both strains can oxidize Sb(III) to Sb(V) under aerobic conditions. The arsenite oxidase (aioA) gene, which might be involved in As(III) and Sb(III) oxidation, was detected in the isolated strains. This study demonstrated that the versatile bacteria with potential applications for bioremediation of As and Sb could be obtained from an easily accessible microbiological source.
Antimony enhances c-Myc stability in prostate cancer via activating CtBP2-ROCK1 signaling pathway
2018, Ecotoxicology and Environmental Safety
Citation Excerpt :
Additionally, increased mortality from lung cancer has been observed in people working in smelters (Gerhardsson et al., 1982). Moreover, antimony trioxide was classified as possible carcinogen (Group 2B) in humans in 1989 by the International Agency for Research on Cancer (IARC) (Léonard, 1996). However, another study argued that antimony exposure has no effect on the mortality of lung cancer (Jones, 1994).
Antimony, one of the heavier pnictogens, is widely used in industry, and its toxicity has become a major concern. Although previous studies suggested that antimony might be a tumorigenic risk factor in several cancers, the molecular basis underlying antimony-mediated transformation remains unclear. Our results showed that the serum concentration of antimony was higher in prostate cancer specimens relative to that of benign prostate tissues, and this high serum concentration of antimony was closely associated with poorer outcome in prostate cancer patients. Additionally, we demonstrated that antimony could promote prostate cancer cell growth in vitro and in vivo. In order to gain insight into the potential mechanisms, we examined the effects of antimony exposure on downstream signaling that could contribute to tumor development. We found that low-dose antimony could regulate the expression of Ctbp2 by binding and regulating the activity of its MRE domain. Meanwhile, CtBP2 could transcriptionally regulate the expression of RhoC, which is a member of the RhoGTPase family. Subsequently, the kinase activity of ROCK1 is increased, which promotes the stability of oncogene c-Myc. Overall, our study demonstrated that antimony could enhance c-Myc protein stability and promote prostate cancer cell proliferation through activating CtBP2-ROCK1 signaling pathway. These findings also substantially highlighted the potential of targeting molecules within antimony induced CtBP2-c-Myc signaling pathway as a promising therapeutic approach for the treatment of prostate cancer.
Solid phase microextraction method using a novel polystyrene oleic acid imidazole polymer in micropipette tip of syringe system for speciation and determination of antimony in environmental and food samples
2018, Talanta
A simple, rapid and sensitive solid phase microextraction method was used for the speciation of inorganic antimony (Sb) by using a novel synthesized polymeric material in micropipette tip of syringe system. In present methodology, the specie of Sb (III) made hydrophobic complex with diethyl dithiocarbamate (DDTC) at pH 5.5 and subsequently adsorbed on polystyrene oleic acid imidazole polymer (POIP), whereas Sb(V) did not made complex and adsorbed on the polymer, remained in aqueous solutions. The strategy of multivariate was carried out to screen out the different variables and assessed the optimum values of their experimental values for the extraction efficiency of analyte. Then the analyte was sorbed on the polymer in micropipette tip of syringe system was quantitatively eluted by different types of acids at different levels for 2–6 aspirating/dispensing cycles. The extracted Sb(III) ions with modifiers were directed into the graphite furnace atomic absorption spectrometry for analysis. The limit of detection (LOD), limit of quantification (LOQ) and preconcentration factor (PF) for Sb(III) was found to be 6 ng L⁻¹, 20 ng L⁻¹ and 100. The RSD value was found to be 4.2%. The standard addition method and certified reference materials were checked for accuracy and validity of method. The developed method was effectively applied for the determination of total and inorganic species of Sb(III) and Sb(V) in different types of water samples, whereas only total Sb was determined in acid digested soil, Tuna fish, rice, spinach, black tea, mixed fruit juice and ice tea samples.
The promotion on cell growth of androgen-dependent prostate cancer by antimony via mimicking androgen activity
2018, Toxicology Letters
Citation Excerpt :
Accumulating clinical studies also demonstrated that antimony exposure was associated with cardiovascular, cerebrovascular, and peripheral arterial diseases (Tubek, 2006). In addition, antimony trioxide was classified as possibly carcinogenic to humans (Group 2B) in 1989 by IARC (Leonard and Gerber, 1996). Increased mortality of lung cancer has been observed in people working in smelters, and inhalation exposure to antimony compounds also caused lung tumors in rodents (Gerhardsson et al., 1985).
Antimony is a widely used heavier pnictogens in industry, and its toxicity has been a matter of concern. Although previous studies have suggested that antimony may have the function as either a tumor suppressor or an oncogene in several cancers, the molecular basis underlying antimony-mediated transformation is still unclear. In the current study, we attempt to elucidate the potential role of antimony in the development of prostate cancer. Our results showed that the concentration of antimony was much higher in serum of prostate cancer patients, and was closely associated with poor outcome of patients who underwent radical prostatectomy. Additionally, low dose of antimony could promote proliferation and invasion of androgen-dependent prostate cancer cell line LNCaP cells in vitro and in vivo. The mechanistic studies demonstrated that exposure to antimony triggered the phosphorylation of androgen receptor (AR), which transcriptionally regulates the expression of androgen-related targets, including PSA and NKX3.1. Overall, our results unearthed that antimony could promote tumor growth by mimicking androgen activity in androgen-dependent prostate cancer cells. Therefore, these findings expanded our understanding on the molecular mechanism of antimony in tumorigenesis and tumor progression of prostate cancer, and it appears to be an inspiring strategy to restrain prostate cancer by inhibiting antimony-induced androgen-like effects.
Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury
2017, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
More interestingly experimental studies and case-reports suggest that antimony toxicity may cause peripheral neurotoxicity (Wahdan et al., 2015) and cerebellar ataxia (Khalil et al., 2006) as well. Whether antimony brings about tumorigenic and teratogenic effects have been less understood (Léonard and Gerber, 1996). A meta-analysis of four comparisons demonstrated higher levels of antimony in hair of patients with autism (n = 181) compared to that of control (n = 185) subjects.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals. Therefore the objective of this study was to investigate the difference in heavy metal measures between patients with ASD and control subjects.
We included observational studies that measured levels of toxic metals (antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium) in different specimens (whole blood, plasma, serum, red cells, hair and urine) for patients with ASD and for controls. The main electronic medical database (PubMed and Scopus) were searched from inception through October 2016.
52 studies were eligible to be included in the present systematic review, of which 48 studies were included in the meta-analyses. The hair concentrations of antimony (standardized mean difference (SMD) = 0.24; 95% confidence interval (CI): 0.03 to 0.45) and lead (SMD = 0.60; 95% confidence interval (CI): 0.17 to 1.03) in ASD patients were significantly higher than those of control subjects. ASD patients had higher erythrocyte levels of lead (SMD = 1.55, CI: 0.2 to 2.89) and mercury (SMD = 1.56, CI: 0.42 to 2.70). There were significantly higher blood lead levels in ASD patients (SMD = 0.43, CI: 0.02 to 0.85). Sensitivity analyses showed that ASD patients in developed but not in developing countries have lower hair concentrations of cadmium (SMD = − 0.29, CI: − 0.46 to − 0.12). Also, such analyses indicated that ASD patients in developing but not in developed lands have higher hair concentrations of lead (SMD = 1.58, CI: 0.80 to 2.36) and mercury (SMD = 0.77, CI: 0.31 to 1.23). These findings were confirmed by meta-regression analyses indicating that development status of countries significantly influences the overall effect size of mean difference for hair arsenic, cadmium, lead, and mercury between patients with ASD and controls.
The findings help highlighting the role of toxic metals as environmental factors in the etiology of ASD, especially in developing lands. While there are environmental factors other than toxic metals that greatly contribute to the etiology of ASD in developed lands. It would be, thus, expected that classification of ASD includes etiological entities of ASD on the basis of implication of industrial pollutants (developed vs. developing ASD).

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Research paperMutagenicity, carcinogenicity and teratogenicity of antimony compounds

Abstract

Coastal Shelf Sci.

Lancet

Toxic. Appl. Pharmacol.

Mutation Res.

Mutation Res.

Mutation Res.

Mutation Res.

Fundam. Appl. Toxicol.

Tuber. Lung. Dis.

The metals 2 Antimony

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity

Environ. Health Perspect

Antimony

Antimony

Utilisation des radionucléides artificiesl (125Sb. 137Cs, 134Cs) pour l'observation (1983–1986) des déplacements des masses d'eau en Manche

Atmospheric trace metals: global cycle and assessment of man's impact

Geochim. Cosmochim. Acta

Composition and size distribution of particles released in refuse incineration

Environ. Sci. Technol.

Toxic trace elements associated with airborne particulate matter: a review

J. Air Pollut. Control Assoc.

Environmental Chemistry of the Elements

Trace elements in plant foodstuffs

Metal accumulation in the food chain and load of feed and foods

Toxicological Profile of Antimony

Reverse transcriptase activity (RTA) in lymphocyte cultures of AIDS patients treated with HPA-23

AIDS Res.

Suppressive effect of polyoxometalates on the cytopathogenenicity of human immunodeficiency virus type 1 (HIV-1) in vitro and their inhibitory activity against HIV-1 reverse transcriptase

Chem. Pharm. Bull. Tokyo

The toxicity of antimony

Ind. Med. Surg

Effects of metals on domestic animals

The work of an occupational hygiene service in environmental control

Ann. Occup. Med.

Research paper
Mutagenicity, carcinogenicity and teratogenicity of antimony compounds

Utilisation des radionucléides artificiesl (¹²⁵Sb. ¹³⁷Cs, ¹³⁴Cs) pour l'observation (1983–1986) des déplacements des masses d'eau en Manche