Metabolomic and proteomic biomarkers for III-V semiconductors: chemical-specific porphyrinurias and proteinurias.

摘要: A pressing need exists to develop and validate molecular biomarkers assess the early effects of chemical agents, both individually in mixtures. This is particularly true for new chemically intensive industries such as semiconductor industry. Previous studies from this laboratory others have demonstrated element-specific alterations heme biosynthetic pathway III-V semiconductors gallium arsenide (GaAs) indium (InAs) with attendant increased urinary excretion specific precursors. These data represent an example a metabolomic biomarker early, before clinical disease develops. that intratracheal or subcutaneous administration GaAs InAs particles hamsters produces induction major stress protein gene families renal proximal tubule cells. was monitored by 35-S methionine labeling products followed two-dimensional gel electrophoresis after exposure particles. The present examined whether these were associated development compound-specific proteinuria 10 30 days following injection hamsters. results GaAs- InAs-specific cell expression patterns varied at days. At 30-day point, cells received showed marked attenuation expression, suggesting inhibition response. changes silver staining. intensity between 10- points most pronounced animals treatment group. No overt morphologic signs death seen animals. Western blot analyses urines antibodies 32-, 70-, 90-kDa did not show presence molecules, indicating proteins excreted urine samples. suggest observed result chemical-specific proteinurias produced cellular toxicity. findings hypothesis involving interference chaperoning reabsorbed proteosomic degradation probable damaged intracellular into filtrate. Overall, provide further information on nephrotoxicity compounds. They also use staining potentially useful proteomic approach damage relation proteotoxicity kidney