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Chronic Exposure to Lead Chromate Causes Centrosome Abnormalities and Aneuploidy in Human Lung Cells

¹ Wise Laboratory of Environmental and Genetic Toxicology, ² Maine Center for Toxicology and Environmental Health, and ³ Department of Applied Medical Science, University of Southern Maine, Portland, Maine and ⁴ The Tumor Biology Program, Division of Experimental Pathology, Mayo Clinic and Foundation, Rochester, Minnesota

Requests for reprints: John Pierce Wise, Sr., University of Southern Maine, 96 Falmouth Street, 178 Science Building, Portland, ME. Phone: 207-228-8050; Fax: 207-228-8057; E-mail: John.Wise{at}usm.maine.edu.

Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens. The carcinogenicity of Cr(VI) is related to its solubility, with the most potent carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One possible explanation is that particulates may provide more chronic exposures to chromate over time. We found that aneuploid cells increased in a concentration- and time-dependent manner after chronic exposure to lead chromate. Specifically, a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour exposure to 0.5 and 1 µg/cm² lead chromate induced 55% and 60% aneuploid metaphases, respectively. We also found that many of these aneuploid cells were able to continue to grow and form colonies. Centrosome defects are known to induce aneuploidy; therefore, we investigated the effects of chronic lead chromate exposure on centrosomes. We found that centrosome amplification in interphase and mitotic cells increased in a concentration- and time-dependent manner with 0.5 and 1 µg/cm² lead chromate for 120 hours, inducing aberrant centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells, respectively; however, lead oxide did not induce centrosome amplification in interphase or mitotic cells. There was also an increase in aberrant mitosis after chronic exposure to lead chromate with the emergence of disorganized anaphase and mitotic catastrophe. These data suggest that one possible mechanism for lead chromate–induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy. (Cancer Res 2006; 66(8): 4041-8)

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				H. Xie, A. L. Holmes, S. S. Wise, S. Huang, C. Peng, and J. P. Wise Sr. Neoplastic Transformation of Human Bronchial Cells by Lead Chromate Particles Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 544 - 552. [Abstract] [Full Text] [PDF]