Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca(2+), changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs).
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PMID:Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro. 1723 15

One of the most notorious environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), easily accumulates in the environment and most organisms, including humans, because of its high lipophilicity and resistance to degradation. TCDD exposure causes a variety of adverse health effects in humans including immunotoxicity, hepatotoxicity, neurotoxicity, and carcinogenesis. For the most part, studies regarding the adverse effects of TCDD on the central nervous system (CNS) have been limited to neurodevelopmental processes. In this study, we investigated the neurotoxicity of TCDD in neuronal cells using a neuroblastoma cell line (clone N2a) and explored the possible mechanisms of action. MTT and Comet assays were conducted to determine if TCDD is cytotoxic and if it causes DNA damage, respectively. The results of these assays revealed that treatment with 100, 300, 500 and 1000 nM TCDD decreased the viability of N2a cells and increased DNA damage in a dose-dependent manner compared to controls. Additionally, a malondialdehyde (MDA) assay was performed to determine if TCDD induces lipid peroxidation. The results of this assay revealed that 100, 300 and 500 nM TCDD induced lipid peroxidation in a dose-dependent manner. Finally, TCDD neurotoxicity (300 nM or higher) in N2a cells was accompanied by elevated intracellular calcium levels. These increased calcium levels increased the phosphorylation of tau via up-regulation of phospho-glycogen synthase kinase-3beta (GSK-3beta). Taken together, these results indicate that TCDD exposure induces neurotoxicity in N2a cells by increasing DNA damage, oxidative stress and intracellular calcium levels. The TCDD-mediated increase of tau phosphorylation in particular indicates an important role for tau hyperphosphorylation in TCDD-induced neurotoxicity.
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PMID:2,3,7,8-TCDD neurotoxicity in neuroblastoma cells is caused by increased oxidative stress, intracellular calcium levels, and tau phosphorylation. 1899 33