Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity

Holmes, Amie L.; Wise, Sandra S.; Xie, Hong; Gordon, Nancy; Thompson, W. Douglas; Wise, John Pierce

doi:10.1016/j.taap.2004.08.006

Cited by 41 publications

(48 citation statements)

References 23 publications

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“…It is established that lead chromate partially dissolves outside the cell, releasing Pb and Cr ions that then enter the cell (9). Once inside the cell, the Cr ions induce the cytotoxic, growth-inhibiting, and genotoxic effects observed after exposure to lead chromate and the lead ions have no apparent effect (14,15,17,18). Thus far, the potential effects of Cr ions on centrosome amplification have not been studied, but a 30-hour exposure to soluble chromate induced aneuploidy, which suggests that Cr ions could have the capacity to cause centrosome amplification, although that study did not consider it (31).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, it is possible that lead ions could contribute to lead chromate-induced centrosome amplification. Studies show that lead ions do enter the cell after lead chromate exposure (17), and a recent study by Bonacker et al showed that soluble lead ions disrupt microtubule function and formation (34). However, lead's effect on centrosome function is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Cr(III), one of the intermediates or some combination of them induce chromosomal aberrations, adducts, cross-links, and strand breaks (7,8,11,12,37). It has been proposed that this genetic damage may result in mutations and ultimately carcinogenesis (17). However, it seems that not only does lead chromate damage DNA, but it also has a significant effect on centrosome and chromosome number.…”

Section: Discussionmentioning

confidence: 99%

“…The internalized Cr ions induce chromosome aberrations, DNA adducts, and DNA double-strand breaks (10)(11)(12)(13)(14)(15), whereas the internalized Pb ions are generally nongenotoxic (8,16). Two studies investigating potential epigenetic effects of Pb in lead chromate-induced carcinogenesis also show that Pb does not interfere with Crinduced cell death (17) or cause mitotic stimulation of Cr-damaged cells (18). In addition, internalized particles seem to have no toxic effect except for possibly a small contribution to cytotoxicity (17).…”

Section: Introductionmentioning

confidence: 99%

“…Two studies investigating potential epigenetic effects of Pb in lead chromate-induced carcinogenesis also show that Pb does not interfere with Crinduced cell death (17) or cause mitotic stimulation of Cr-damaged cells (18). In addition, internalized particles seem to have no toxic effect except for possibly a small contribution to cytotoxicity (17). Thus, the differences between particulate and soluble exposures remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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 Mg/cm 2 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 Mg/cm 2 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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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The genotoxicity of particulate and soluble chromate in sperm whale (physeter macrocephalus) skin fibroblasts

Wise

LaCerte

et al. 2011

Environ and Mol Mutagen

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Hexavalent chromium is a marine pollutant of concern, both for the health of ocean ecosystems and for public health. Hexavalent chromium is known to induce genotoxicity in human and other terrestrial mammals. It is also known to be present in both water and air in the marine environment. However, currently there are limited data concerning both chromium levels and its toxicological effects in marine mammals. This study investigated the cytotoxic and genotoxic effects of soluble and particulate hexavalent chromium in sperm whale skin fibroblasts. Both forms of hexavalent chromium induced concentration-dependent increases in cytotoxicity and genotoxicity indicating that these compounds can be a health risk if the whales are exposed to them. These data support a hypothesis that chromium is a concern in the marine environment in general and for the health of sperm whales in particular.

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Human lung cell growth is not stimulated by lead ions after lead chromate-induced genotoxicity

et al. 2005

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Chromate compounds are known human lung carcinogens. Water solubility is an important factor in the carcinogenicity of these compounds with the most potent carcinogenic compounds being water-insoluble or 'particulate'. Previously we have shown that particulate chromates dissolve extracellularly releasing chromium (Cr) and lead (Pb) ions and only the Cr ions induce genotoxicity. Pb ions have been considered to have epigenetic effects and it is thought that these may enhance the carcinogenic activity of lead chromate, perhaps by stimulating Cr-damaged cells to divide. However, this possibility has not been directly tested. Accordingly, we investigated the ability of Pb ions to stimulate human lung cells and possibly force lead chromate-damaged cells to grow. We found that at concentrations of lead chromate that induced damage, human lung cells exhibited cell cycle arrest and growth inhibition that were very similar to those observed for sodium chromate. Moreover, we found that soluble Pb ions were not growth stimulatory to human lung cells and in fact induced progressive mitotic arrest. These data indicate that lead chromate-generated Cr ions cause growth inhibition and cell cycle arrest and that Pb does not induce epigenetic effects that stimulate chromate-damaged cells to grow.

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Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity

Cited by 41 publications

References 23 publications

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

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

The genotoxicity of particulate and soluble chromate in sperm whale (physeter macrocephalus) skin fibroblasts

Human lung cell growth is not stimulated by lead ions after lead chromate-induced genotoxicity

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