Disease relevance of TRINICKEL DISULFIDE

• Rhabdomyosarcomas were locally induced by one im injection of Ni or Ni subsulfide [(Ni3S2) CAS: 12035-72-2] dust in the hind leg of WAG rats [1].
• Sarcomas in mice were induced by i.m. and s.c. administration of 63Ni- and 35S-labeled nickel subsulfide (Ni3S2), and the fate of the Ni3S2 was studied in tumors and normal tissues during carcinogenesis [2].
• Inhalation of particulate nickel subsulfide (Ni3S2) causes chronic active inflammation and fibrosis of the lungs [3].
• In rats, an intrarenal injection of nickel subsulfide (Ni3S2) regularly caused, within 2 months, an erythrocytosis and eventually a renal carcinoma in 40 per cent of the animals [4].
• The influence upon nickel subsulfide (alpha-Ni3S2; Ni-SS)-induced carcinogenesis in the soft tissue of bone fracture at the site of Ni-SS exposure was studied using female Fischer rats [5].

Psychiatry related information on TRINICKEL DISULFIDE

• Dose-response and time-response study of erythrocytosis in rats after intrarenal injection of nickel subsulfide [6].

High impact information on TRINICKEL DISULFIDE

• Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide [7].
• Nickel subsulfide (0.15 and 1 mg/m3) and nickel oxide (1.25 and 2.5 mg/m3) caused an exposure-related increased incidence of alveolar/bronchiolar neoplasms and adrenal medulla neoplasms in male and female rats [8].
• None (0 of 10) of the nickel subsulfide and iron-induced RMTs and only 1 of 10 DMN-OMe-induced tumors that were evaluated contained point mutations within this portion of the p53 gene [9].
• GGT to GTT transversions in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide or nickel subsulfide/iron are consistent with oxidative damage to DNA [10].
• The effects of nickel subsulfide (Ni3S2) and nickel chloride [Ni(II)] on hydroxylation and deglycosylation of pure 2'-deoxyguanosine (dG) and on hydroxylation of guanine (Gu) residues in calf thymus DNA in the absence or presence of hydrogen peroxide (H2O2) and/or ascorbate (Ascb) were studied with the use of high-performance liquid chromatography [11].

Chemical compound and disease context of TRINICKEL DISULFIDE

• I.m. administration of MgCarb mixed with Ni3S2 up to the Mg/Ni molar ratio of 1.0 inhibited the carcinogenicity of Ni3S2 in a dose-related manner; final incidence of sarcomas decreased from 100 to 55% and the appearance of first tumors was delayed from 25 to 39 weeks [12].
• Comparative toxicity of nickel oxide, nickel sulfate hexahydrate, and nickel subsulfide after 12 days of inhalation exposure to F344/N rats and B6C3F1 mice [13].
• In experimental animals, Dithiocarb has an inhibitory effect on the production of rat rhabdomyosarcomas induced by the intramuscular implantation of nickel subsulfide, and N-methyl formamide inhibits the growth of transplantable nickel fibromas in rats [14].
• SiO2 and Ni3S2 both caused dose-dependent acute toxicity as assessed by LDH and CV, and caused alterations in nuclear morphology consistent with apoptosis [15].
• Manganese inhibition of nickel subsulfide induction of erythrocytosis in rats [16].

Biological context of TRINICKEL DISULFIDE

• Phagocytosis of nickel subsulfide particles during the early stages of neoplastic transformation in tissue culture [17].
• Oncogenic transformation and cell lysis in C3H/10T 1/2 cells and increased sister chromatid exchange in human lymphocytes by nickel subsulfide [18].
• Distinct mechanisms of oxidative DNA damage induced by carcinogenic nickel subsulfide and nickel oxides [19].
• The U.S. National Toxicology Program has shown clear evidence of carcinogenicity of nickel subsulfide (Ni(3)S(2)) and some evidence of carcinogenicity of NiO (green) in rats [19].
• The effects of magnesium carbonate on the cytotoxicity and genotoxicity induced by nickel subsulfide were examined with respect to the inhibition of cell proliferation, micronuclei formation, DNA-protein cross-link formation, and intranuclear nickel concentration [20].

Anatomical context of TRINICKEL DISULFIDE

• The carcinogenicity of nickel subsulfide, Ni3S2, for respiratory tract epithelium was studied in heterotopic tracheal transplants with doses of 1 and 3 mg Ni3S2 per trachea [21].
• Carcinogenicity of nickel subsulfide for respiratory tract mucosa [21].
• Nickel subsulfide in moderate doses caused morphological transformation to type I, II, and III foci and induced long microvilli on the cells in the transformed cultures, demonstrating oncogenic transforming ability [18].
• Nickel subsulfide (Ni3S2) was injected in various amounts into the testis of adult Fischer rats for the study of the acute and chronic effects of Ni3S2 on testicular cells [22].
• Nickel subsulfide, alpha Ni3S2, was a notable exception to the general concordance between phagocytic indices and dissolution half-times: alpha Ni3S2 was avidly phagocytized by macrophages, yet it had one or the shortest dissolution half-times [23].

Associations of TRINICKEL DISULFIDE with other chemical compounds

• The effects of magnesium carbonate (MgCarb) on carcinogenesis and natural killer (NK) cell modulation by nickel subsulfide (Ni3S2) were studied [12].
• Application of cross-chemical and cross-endpoint comparisons suggest that, for chronic inhalation exposure, nickel sulfate appears to be as toxic or more toxic than nickel subsulfide and nickel oxide, although the high response rates for the latter two compounds at the lowest chronically administered concentration make such conclusions problematic [24].
• The potent protective effects of these specific amino acids against nickel subsulfide-induced DPXL formation in isolated rat lymphocytes may be due in part to impaired cellular uptake of Ni(2+), inhibition of the binding of Ni(2+) to deproteinized DNA, and a reduction in reactive oxygen species [25].
• Nickel subsulfide and nickel monosulfide were taken into cells by phagocytosis, since particles were visible in intracytoplasmic vacuoles [26].
• Furthermore, coincubation of 2 mM nickel subsulfide with catalase, dimethylthiourea, mannitol, or vitamin C at 37 degrees C for 2 h resulted in a significant decrease of nickel subsulfide-induced formation of DPXLs, suggesting that nickel subsulfide-induced DPXLs formation in isolated rat lymphocytes is caused by the formation of ROS [25].

Gene context of TRINICKEL DISULFIDE

• Metallothionein-I/II double knockout mice are no more sensitive to the carcinogenic effects of nickel subsulfide than wild-type mice [27].
• At the cellular level, particulate nickel subsulfide inhibits fibrinolysis by transcriptionally inducing expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of the urokinase-type plasminogen activator [28].
• Since the urokinase-type plasminogen activator (uPA) initiates this cascade, this hypothesis was tested by investigating the effects of noncytotoxic levels of nickel subsulfide on the balance of uPA expression relative to expression of its inhibitor, PAI-1, in cultured human bronchial epithelial cells (BEAS-2B) [29].
• A decrease of up to > 90% in Fhit protein levels was also observed in 22 local sarcomas (mostly fibrosarcomas) induced by i.m. injection of nickel subsulfide in C57BL/6 and MT+ (C57BL/6 overexpressing metallothionein) mice, as compared with normal muscles [30].
• Normal human fibroblasts, preincubated with nickel subsulfide for 46 hr followed by a coincubation of nickel subsulfide and BPDE for 2 hr, showed a dramatic reduction in the mutant frequency of the hypoxanthine (guanine)phosphoribosyl-transferase (HPRT) gene when compared to cells treated only with BPDE [31].

Analytical, diagnostic and therapeutic context of TRINICKEL DISULFIDE

• Fate of nickel subsulfide during carcinogenesis studied by autoradiography and X-ray powder diffraction [2].
• We subsequently applied the comet assay and transgenic rodent mutation assays to investigate the DNA damaging effect and mutagenic potential of nickel subsulfide in target cells of carcinogenesis [32].
• Soluble nickel was negative in an NTP inhalation bioassay, while there was some evidence for tumorigenicity in rats for less soluble nickel oxide, and there was clear evidence for tumorigenicity of insoluble nickel subsulfide in rats [33].
• Groups of 25 male MT-transgenic and wild type (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni3S2) in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age and were observed for 104 weeks [34].
• These radioimmunoassays confirm previous bioassays findings that serum epo concentrations are significantly increased in rats with Ni3S2-induced erythrocytosis [35].

References