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

Hexavalent chromium [Cr(VI)] is a genotoxic carcinogen for which inhalation is a major potential route of exposure in occupational settings. In the pr esent study, the ability of sodium dichromate to cause DNA strand breaks in three populations of cells, human whole blood cells, isolated human periph eral blood lymphocytes and cultured A549 lung epithelial cells, was investi gated. Treatment with non-cytotoxic concentrations of sodium dichromate (fo r 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) i ncrease in the number of DNA strand breaks were 500, 50 and 10 <mu>M, respe ctively, in these cells. The use of formamidopyrimidine glycosylase increas ed the sensitivity of detection of strand breaks in A549 cells 10-fold, sug gesting a role for DNA base oxidation in the mechanism of dichromate-induce d DNA strand breaks. In support of this hypothesis, immunocytochemistry ind icated an elevation of 8-oxodeoxyguanosine in A549 cells treated with 10 an d 500 muM sodium dichromate for 1 h. We also demonstrated 2.11- and 2.5-fol d ranges in the level of control and dichromate (500 muM)-induced DNA stran d breaks, respectively, in cells of whole blood within a group of healthy v olunteers (n = 26). A statistically significant (P < 0.001) positive Pearso n'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 agai nst the formation of dichromate-induced DNA strand breaks.