Human lung cell growth is not stimulated by lead ions after lead chromate-induced genotoxicity
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.
Key Wordschromate cytotoxicity lead particulate
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- 1.IARC: Chromium, nickel and welding. Monographs on the Evaluations of Carcinogenic Risk to Humans, 49: 1–648, 1990Google Scholar
- 4.Patierno SR, Banh D, Landolph JR: Transformation of C3H/10T1/2 mouse embryo cells by insoluble lead chromate but not soluble calcium chromate: Relationship to mutagenesis and internalization of lead chromate particles. Cancer Res 47: 3815–3823, 1988Google Scholar
- 5.Ishikawa Y, Nakagawa K, Satoh Y, Kitagawa T, Sugano H, Hirano T, Tsuchiya E: Characteristics of chromate workers' cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study. Br J Cancer 70: 160–166, 1994aGoogle Scholar
- 6.Ishikawa Y, Nakagawa K, Satoh Y, Kitagawa T, Sugano H, Hirano T, Tsuchiya E: “Hot spots” of chromium accumulation at bifurcations of chromate workers' bronchi. Cancer Res 54: 2342–2346, 1994bGoogle Scholar
- 7.Xie H, Holmes AL, Wise SS, Gordon N, Wise JP Sr: Lead chromate-induced chromosome damage requires extracellular dissolution to liberate chromium ions but does not require particle internalization or intracellular dissolution. Chem Res Toxicol (in press) 2004Google Scholar
- 8.Wise SS, Holmes AL, Ketterer ME, Hartsock WJ, Fomchenko E, Katsifis S, Thompson WD, Wise JP Sr: Chromium is the proximate clastogenic species for lead chromate-induced clastogenicity in human bronchial cells. Mutat Res 560: 79–89, 2004aGoogle Scholar
- 9.Singh J, Pritchard DE, Carlisle DL, Mclean JA, Montaser A, Orenstein JM, Patierno SR: Internalization of carcinogenic lead chromate particles by cultured normal human lung epithelial cells: Formation of intracellular lead-inclusion bodies and induction of apoptosis. Toxicol Appl Pharmol 161: 240–248, 1999CrossRefGoogle Scholar
- 15.Holmes AL, Wise SS, Xie H, Gordon N, Thompson WD, Wise JP Sr: Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity. Toxicol Appl Pharmacol (in press) 2004Google Scholar
- 17.Hartwig A: Role of DNA repair inhibition in lead- and cadmium- induced genotoxicity: A review. Environ Health Perspect 102(Suppl 3): 45–50, 1994Google Scholar
- 27.DeFlora S, Wetterhahn KE: Mechanisms of chromium metabolism and genotoxicity. Life Chem Rep 7: 169–244, 1989Google Scholar