PbCrO4 mediates cellular responses via reactive oxygen species

Stephen S. Leonard, Jenny R. Roberts, James M. Antonini, Vince Castranova, Xianglin Shi

Research output: Contribution to journalReview articlepeer-review

53 Scopus citations


Exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as lead chromate (PbCrO4), has been associated with lung cancer and respiratory tract toxicity. Previous studies indicate that the solubility of Cr(VI)-compounds is an important factor in Cr(VI)-induced carcinogenesis. The present study investigates reactive oxygen species (ROS) generation by PbCrO4 particles and cellular responses using RAW 264.7 cells. A mixture containing PbCrO4 and RAW 264.7 cells generated hydroxyl radical (•OH), using cellularly generated H2O2 as a precursor, as measured by electron spin resonance (ESR) spin trapping in combination with H2O2 and •OH scavengers, catalase and sodium formate. The effect of ascorbic acid on •OH radicals was also measured using ESR. Confocal microscopy showed that particles could become either bound to the cell surface or engulfed over a 120 min time period. H2O2 generation and O2 consumption were also increased after treatment of the cells with PbCrO4. Both NF-κB and AP-1 were activated after exposure to PbCrO4 particles as measured by the NF-κB or AP-1 luciferase reporter plasmid assay. Our investigation thus demonstrated that the RAW 264.7 cells phagocytized the PbCrO4 particles leading to accumulation of the particles within vacuoles in the cytoplasm. These particles could induce chronic production of ROS and activation of NF-κB and AP-1. Such induction of transcription pathways may be involved in the inflammatory and carcinogenic responses induced by Cr(VI)-containing particles.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - Jan 2004


  • AP-1
  • Electron spin resonance (ESR)
  • Hydroxyl radicals
  • NF-κB
  • PbCrO
  • RAW 264.7 cells

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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