Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells

Amie L. Holmes, Sandra S. Wise, Sarah J. Sandwick, Wilma L. Lingle, Vivian C. Negron, W. Douglas Thompson, John Pierce Wise

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4041-4048
Number of pages8
JournalCancer Research
Volume66
Issue number8
DOIs
StatePublished - Apr 15 2006

Fingerprint

Centrosome
Aneuploidy
Lung
Interphase
Carcinogens
Chromates
Anaphase
Metaphase
chromium hexavalent ion
lead chromate
Mitosis
Solubility
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Holmes, A. L., Wise, S. S., Sandwick, S. J., Lingle, W. L., Negron, V. C., Thompson, W. D., & Wise, J. P. (2006). Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells. Cancer Research, 66(8), 4041-4048. https://doi.org/10.1158/0008-5472.CAN-05-3312

Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells. / Holmes, Amie L.; Wise, Sandra S.; Sandwick, Sarah J.; Lingle, Wilma L.; Negron, Vivian C.; Thompson, W. Douglas; Wise, John Pierce.

In: Cancer Research, Vol. 66, No. 8, 15.04.2006, p. 4041-4048.

Research output: Contribution to journalArticle

Holmes, AL, Wise, SS, Sandwick, SJ, Lingle, WL, Negron, VC, Thompson, WD & Wise, JP 2006, 'Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells', Cancer Research, vol. 66, no. 8, pp. 4041-4048. https://doi.org/10.1158/0008-5472.CAN-05-3312
Holmes AL, Wise SS, Sandwick SJ, Lingle WL, Negron VC, Thompson WD et al. Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells. Cancer Research. 2006 Apr 15;66(8):4041-4048. https://doi.org/10.1158/0008-5472.CAN-05-3312
Holmes, Amie L. ; Wise, Sandra S. ; Sandwick, Sarah J. ; Lingle, Wilma L. ; Negron, Vivian C. ; Thompson, W. Douglas ; Wise, John Pierce. / Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells. In: Cancer Research. 2006 ; Vol. 66, No. 8. pp. 4041-4048.
@article{ae3f47a18093453f87b61fb4a619c486,
title = "Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells",
abstract = "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.",
author = "Holmes, {Amie L.} and Wise, {Sandra S.} and Sandwick, {Sarah J.} and Lingle, {Wilma L.} and Negron, {Vivian C.} and Thompson, {W. Douglas} and Wise, {John Pierce}",
year = "2006",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-05-3312",
language = "English (US)",
volume = "66",
pages = "4041--4048",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells

AU - Holmes, Amie L.

AU - Wise, Sandra S.

AU - Sandwick, Sarah J.

AU - Lingle, Wilma L.

AU - Negron, Vivian C.

AU - Thompson, W. Douglas

AU - Wise, John Pierce

PY - 2006/4/15

Y1 - 2006/4/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33646235874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646235874&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-3312

DO - 10.1158/0008-5472.CAN-05-3312

M3 - Article

C2 - 16618723

AN - SCOPUS:33646235874

VL - 66

SP - 4041

EP - 4048

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 8

ER -