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

N. J. Hodges, B. Ádám, A. J. Lee, H. J. Cross, J. K. Chipman

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

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-oxo-deoxyguanosine 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.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalMutagenesis
Volume16
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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