Along with existing and emerging use of nanoscale materials, growing concerns have arisen about their unintentional health and environmental impact. The objective of the ongoing study was to assess the toxicity profile of metal oxide nanoparticles proposed for use in industrial production methodology. Metal oxide nanoparticles used in this study included TiO2, ZnO, Fe3O4, Al2O3, and CrO3 with particle sizes ranging from 30 to 45 nm. Cellular morphology, mitochondrial function, membrane leakage of lactate dehydrogenase (LDH), permeability of plasma membrane, and apoptosis were assessed under controlled and exposed conditions (2 to 72 h of exposure). The microscopic studies demonstrated that nanoparticle-exposed Neuro-2A cells (especially ZnO) at doses >100 microg/mL became abnormal in size, displaying cellular shrinkage, and detachment from the surface of flasks. Mitochondrial function decreased significantly in the cells exposed to ZnO at 50 to 100 microg/mL. However, Fe3O4, Al2O3, and TiO2 had no measurable effect on the cells until the concentrations reached greater than 200 microg/mL. LDH leakage significantly increased in the cells exposed to ZnO (50 to 100 microg/mL), while other nanoparticles tested displayed LDH leakage only at higher doses (>200 microg/mL). Flow cytometer tests showed that apoptosis took place in cells exposed to ZnO nanoparticles. More cells became necrotic as the concentrations increased.

No abstract

During prothrombin biosynthesis, glutamyl residues in prothrombin precursor proteins are carboxylated to gamma-carboxyglutamyl residues by a vitamin K dependent carboxylase. Calcium-dependent and calcium-independent rat prothrombin antibody subpopulations have been produced and utilized to study the liver microsomal precursors of prothrombin that accumulate when vitamin K action is blocked. A substantial portion of the precursor pool accumulating in the vitamin K deficient or warfarin-treated rat will react with a Ca2+-dependent antibody at high calcium concentration and appears to be partially carboxylated. During in vitro incubation in the presence of vitamin K, the fraction of the precursor pool which is tightly bound to the microsomal membrane appears to be the preferred substrate for the vitamin K dependent carboxylation. A small amount of completely carboxylated rather than a large amount of partially carboxylated products are produced during these incubations. Treatment with a Sepharose-bound prothrombin antibody demonstrated that about 20-25% of the total carboxylated microsomal protein precursor pool consists of prothrombin precursors. This treatment removes an equal amount of total carboxylase activity, and the enzyme is active in this carboxylase precursor-antibody complex.

No abstract