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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mishra, Pradyumna Kumar Panwar, Hariom Bhargava, Arpit Gorantla, Venkata Raghuram Jain, Subodh Kumar Banerjee, Smita Maudar, Kewal Krishan |
| Description | Author Affiliation: Mishra PK ( Bhopal Memorial Hospital & Research Centre, Raisen Bypass Road, Bhopal 462 038, India. pkm 8bh@yahoo.co.uk) |
| Abstract | Isocyanates, a group of low molecular weight aromatic and aliphatic compounds containing the isocyanate group (-NCO), are important raw materials with diverse industrial applications; however, pathophysiological implications resulting from occupational and accidental exposures of these compounds are hitherto unknown. Although preliminary evidence available in the literature suggests that isocyanates and their derivatives may have deleterious health effects including immunotoxicity, but molecular mechanisms underlying such an effect have never been addressed. The present study was carried out to assess the immunotoxic response of methyl isocyanate (MIC) on cultured human lymphocytes isolated from healthy human volunteers. Studies were conducted to evaluate both dose-dependent and time-course response (n = 3), using N-succinimidyl N-methylcarbamate, a surrogate chemical substitute to MIC. Evaluation of DNA damage by ataxia telangiectasia mutated (ATM) and gamma H2AX protein phosphorylation states; measure of apoptotic index through annexin-V/PI assay, apoptotic DNA ladder assay, and mitochondrial depolarization; induction of oxidative stress by CM-H2DCFDA and formation of 8-hydroxy-2' deoxy guanosine; levels of antioxidant defense system enzyme glutathione reductase; and multiplex cytometric bead array analysis to quantify the secreted levels of inflammatory cytokines, interleukin-8, interleukin-1beta, interleukin-6, interleukin-10, tumor necrosis factor, and interleukin-12p70 parameters were carried out. The results of the study showed a dose- and time-dependent response, providing evidence to hitherto unknown molecular mechanisms of immunotoxic consequences of isocyanate exposure at a genomic level. We anticipate these data along with other studies reported in the literature would help to design better approaches in risk assessment of occupational and accidental exposure to isocyanates. |
| File Format | HTM / HTML |
| ISSN | 10956670 |
| Issue Number | 6 |
| Volume Number | 22 |
| e-ISSN | 10990461 |
| Journal | Journal of Biochemical and Molecular Toxicology |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2008-11-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Molecular Biology Discipline Biochemistry Discipline Toxicology Apoptosis Drug Effects Dna Damage Inflammation Pathology Isocyanates Pharmacology Lymphocytes Oxidative Stress Annexin A5 Metabolism Antioxidants Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins Cells, Cultured Cytokines Dna Fragmentation Dna-binding Proteins Deoxyguanosine Analogs & Derivatives Enzyme-linked Immunosorbent Assay Fluorescein-5-isothiocyanate Glutathione Reductase Histones Humans Inflammation Mediators Phosphorylation Propidium Protein-serine-threonine Kinases Reactive Oxygen Species Tumor Suppressor Proteins Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Molecular Biology Biochemistry Toxicology Molecular Medicine |
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