Chronic exposure to zinc chromate induces centrosome amplification and spindle assembly checkpoint bypass in human lung fibroblasts

Amie L. Holmes, Sandra S. Wise, Stephen C. Pelsue, Abou El Makarim Aboueissa, Wilma Lingle, Jeffrey L Salisbury, Jamie Gallagher, John Pierce Wise

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen; however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 h exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy, and tetraploidy. Zinc chromate also induced centrosome amplification in a concentrationand time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Furthermore, chronic exposure to zinc chromate induced concentration- and timedependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division, and premature anaphase. Last, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalChemical Research in Toxicology
Volume23
Issue number2
DOIs
StatePublished - Feb 15 2010

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M Phase Cell Cycle Checkpoints
Centrosome
Fibroblasts
Amplification
Lung
Chromosomal Instability
Centromere
Aneuploidy
Chromosomes
Carcinogens
Chromium compounds
Anaphase
Polyploidy
Tetraploidy
zinc chromate
Interphase
Solubility
Defects
chromium hexavalent ion

ASJC Scopus subject areas

  • Toxicology

Cite this

Chronic exposure to zinc chromate induces centrosome amplification and spindle assembly checkpoint bypass in human lung fibroblasts. / Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, Abou El Makarim; Lingle, Wilma; Salisbury, Jeffrey L; Gallagher, Jamie; Wise, John Pierce.

In: Chemical Research in Toxicology, Vol. 23, No. 2, 15.02.2010, p. 386-395.

Research output: Contribution to journalArticle

Holmes, Amie L. ; Wise, Sandra S. ; Pelsue, Stephen C. ; Aboueissa, Abou El Makarim ; Lingle, Wilma ; Salisbury, Jeffrey L ; Gallagher, Jamie ; Wise, John Pierce. / Chronic exposure to zinc chromate induces centrosome amplification and spindle assembly checkpoint bypass in human lung fibroblasts. In: Chemical Research in Toxicology. 2010 ; Vol. 23, No. 2. pp. 386-395.
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