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PbCrO4 mediates cellular responses via reactive oxygen species
Stephen S Leonard1, Jenny R Roberts, James M Antonini
1Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Molecular and Cellular Biochemistry
|February 20, 2004
Summary
Lead chromate (PbCrO4) particles generate reactive oxygen species (ROS) and activate inflammatory pathways in cells. This cellular response to hexavalent chromium (Cr(VI)) may contribute to lung cancer and toxicity.
Area of Science:
- Toxicology
- Cell Biology
- Carcinogenesis
Background:
- Hexavalent chromium (Cr(VI)) compounds, like lead chromate (PbCrO4), are linked to lung cancer.
- Cr(VI) compound solubility influences its carcinogenic potential.
Purpose of the Study:
- Investigate reactive oxygen species (ROS) generation by PbCrO4 particles.
- Examine cellular responses in RAW 264.7 cells exposed to PbCrO4.
Main Methods:
- Electron spin resonance (ESR) with scavengers to measure hydroxyl radical ((.)OH) generation.
- Confocal microscopy to observe particle-cell interactions.
- Luciferase reporter assays to measure NF-kappaB and AP-1 activation.
Main Results:
- PbCrO4 particles induced hydroxyl radical ((.)OH) generation via H2O2.
- RAW 264.7 cells phagocytized PbCrO4, leading to intracellular accumulation.
- PbCrO4 exposure increased ROS production, H2O2 generation, O2 consumption, and activated NF-kappaB and AP-1.
Conclusions:
- PbCrO4 particles induce chronic ROS production and activate key inflammatory transcription factors.
- Phagocytosis of PbCrO4 leads to cellular responses implicated in inflammation and carcinogenesis.