Mutagenesis, Vol. 16, No. 6, 467-474,
November 2001
© 2001 UK Environmental Mutagen Society/Oxford University Press
Induction of DNA-strand breaks in human peripheral blood lymphocytes and A549 lung cells by sodium dichromate: association with 8-oxo-2-deoxyguanosine formation and inter-individual variability
Institute of Occupational Health and 3 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK and 2 Department of Preventive Medicine, School of Public Health, Medical and Health Sciences Center, University of Debreen, H-4012 Debreen, Hungary
Hexavalent chromium [Cr(VI)] is a genotoxic carcinogen for which inhalation is a major potential route of exposure in occupational settings. In the present study, the ability of sodium dichromate to cause DNA strand breaks in three populations of cells, human whole blood cells, isolated human peripheral blood lymphocytes and cultured A549 lung epithelial cells, was investigated. Treatment with non-cytotoxic concentrations of sodium dichromate (for 1 h) resulted in a concentration-dependent increase in the number of DNA strand breaks as measured by the Comet assay. The lowest concentrations of sodium dichromate that resulted in a statistically significant (P < 0.01) increase in the number of DNA strand breaks were 500, 50 and 10 µM, respectively, in these cells. The use of formamidopyrimidine glycosylase increased the sensitivity of detection of strand breaks in A549 cells 10-fold, suggesting a role for DNA base oxidation in the mechanism of dichromate-induced DNA strand breaks. In support of this hypothesis, immunocytochemistry indicated an elevation of 8-oxodeoxyguanosine in A549 cells treated with 10 and 500 µM sodium dichromate for 1 h. We also demonstrated 2.11- and 2.5-fold ranges in the level of control and dichromate (500 µM)-induced DNA strand breaks, respectively, in cells of whole blood within a group of healthy volunteers (n = 26). A statistically significant (P < 0.001) positive Pearson's correlation (r = 0.606) was found between control and treated levels of DNA strand breaks, suggesting that factors responsible for relatively low levels of DNA strand breaks in untreated PBL may also offer protection against the formation of dichromate-induced DNA strand breaks.
1 To whom correspondence should be addressed. Tel: +44 121 414 6016; Fax: +44 121 414 6217; Email: n.hodges{at}bham.ac.uk
* The first three authors contributed eually to this work
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