Metal ions in human cancer development.
ABSTRACT Metals have been in the environment during the entire evolution of man and the use of metals is key to human civilization. None-the-less, several very toxic species are included in the metallic elements and compounds either widely used by man and/or widely found in the human environment. This includes the five metallic agents considered human carcinogens, namely arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, chromium(VI) compounds, and nickel compounds, all of which are proven carcinogens in laboratory animals as well. There is significant human exposure to these carcinogenic inorganics, either occupationally, through the environment, or both. Inhalation is typical in the workplace while inhalation or ingestion occurs from environmental sources. Human metallic carcinogens frequently cause tumors at the portal of entry and lung cancers are the most common tumor after inhalation. Agent-specific tumors occur as well, like urinary bladder tumors after arsenic exposure, which are due to biokinetics or mechanisms that are specific to arsenic. Even in their simplest elemental form, metals are not inert, and they have biological activity. However, it should be kept in mind that these inorganic carcinogens, when in the atomic form, cannot be broken down into less toxic subunits, and this, in part, is why they are so important as environmental human carcinogens. This chapter focuses on the metallic agents that are known human carcinogens.
SourceAvailable from: Vasil Atanasov
Article: STUDY ON LEVELS OF Cu IN LIVER, OVARIES, TESTES AND MUSCULATURE OF HYDROBIONTS FROM WATERBODIES IN STARA ZAGORA REGION, BULGARIA. E. Valkova, V. Atanasov, B. Bivolarski*, N. Bozakova*, P. Valkova Thrakia University, Faculty of Agriculture – Stara Zagora * Thrakia University, Faculty of Veterinary Medicine – Stara Zagora[Show abstract] [Hide abstract]
ABSTRACT: The concentrations of the element Cu were determined in liver, ovaries, testes and musculature by common carp (Cyprinus carpio L.) as well as in musculature by mussel Dreissena polymorpha from 3 waterbodies in Stara Zagora region using atomic absorption spectrometry. The sampling was carried out in two studied period: from May to December 2010 and from May to August 2011. The levels of the investigated element Cu (copper) are higher in the liver than in the musculature of studied fish species (liver of carps from Ovcharica Dam - concentration of Cu - 9, 99 mg / kg and musculature – 0, 68 mg/kg for the period from May to December 2010). Such an accumulation (but to lower degree) for that heavy element is observed in fish gonads (ovaries of carps from Ovcharica Dam - 4, 8 mg/kg for the period from May to August 2011). The results of copper content studies in the liver, ovaries, testes and musculature of hydrobionts caught by the aforementioned waterbodies in the period May -December 2010 confirm those of the period May - August 2011. Since the established values of Cu were significantly lower in musculature, ovaries and testes of hydrobionts of studied waterbodies, a more reliable biological indicator is a liver of aquabionts. As an organ with the highest metabolic workload, it has accumulated high levels of heavy metals during the live and could be used as an object of a retrospective ecological- biochemical monitoring. Key words: liver, ovaries, testes, musculature, Cyprinus carpio L., Dreissena polymorpha, waterbodies.
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ABSTRACT: Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53-5.21, p dominant < 0.001]. The A/G allele carriers at rs28366003 MT2A were at higher risk of SCLC development (OR = 2.63, 95 % CI 1.41-2.85, p < 0.001]. There was a significant association between the rs28366003 and stage and TFG classification. Most carriers of minor allele had a higher stage (OR = 2.76, 95 % CI 1.11-7.52, p = 0.03), increased cancer aggressiveness, as defined by a higher total TFG score (>18 points) (OR = 3.76, 95 % CI 1.15-12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72-44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.Medical Oncology 07/2014; 31(7):75. DOI:10.1007/s12032-014-0075-8 · 2.06 Impact Factor
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ABSTRACT: Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2T of SCC and NCM samples, respectively. As a result, a significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that -5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer.Toxicology and Applied Pharmacology 08/2014; 280(2). DOI:10.1016/j.taap.2014.08.016 · 3.98 Impact Factor