Cell-enhanced dissolution of carcinogenic lead chromate particles: The role of individual dissolution products in clastogenesis

John Pierce Wise, Diane M. Stearns, Karen E. Wetterhahn, Steven R. Patierno

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Lead chromate induces chromosomal damage as a result of extracellular dissolution producing solubilized chromium and lead and we show here that the dissolution process is greatly accelerated by the presence of cells. We have sought to determine which of these ions is involved in lead chromate-induced clastogenicity. Cell-mediated extracellular dissolution of participate lead chromate resulted in the accumulation of both solubilized chromium and solubilized lead, reaching concentrations in the extracellular medium of 15 and 1.9 μ.M respectively and reaching concentrations inside the cell of 2700 and 97 (μM respectively. Both the extracellular and intracellular accumulation of chromium was time dependent and both the solubilized lead and chromium increased proportionately from a lower dose to a higher dose. Exposing cells to water soluble sodium chromate under conditions which produced similar time-dependent intracellular concentrations of chromium also produced a similar amount and spectrum of chromosome damage as lead chromate. In contrast, exposure to lead glutamate resulted in intracellular lead levels 438-times higher than those produced by lead chromate, but produced no chromosome damage. A higher dose of lead glutamate was weakly clastogenic, but it induced a different spectrum of chromosomal aberrations than lead chromate. Pretreatment of cells with vitamin E had no effect on the uptake of chromium, but reduced both sodium chromateand lead chromate-induced clastogenesis by 54-93%. Vitamin E pretreatment did not affect lead glutamateinduced clastogenesis. The results of this study indicate that although lead(II) is weakly clastogenic at high doses, hexavalent chromium is the proximate clastogen in lead chromate-induced clastogenesis. Additionally, this is the first report that pretreatment of cells with vitamin E can block clastogenesis induced by particulate chromates.

Original languageEnglish (US)
Pages (from-to)2249-2254
Number of pages6
JournalCarcinogenesis
Volume15
Issue number10
DOIs
StatePublished - Oct 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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