Hexavalent chromium produces DNA strand breakage but not unscheduled DNA synthesis at sub-cytotoxic concentrations in hepatocytes.
Rat hepatocytes were used to investigate the possible induction of unscheduled DNA synthesis (UDS) and the extent of DNA strand breaks induced by sodium dichromate (a representative chromium(VI) compound) and chromium acetate hydroxide (chromium(III)) in vitro. Cytotoxicity, measured using tetrazolium salt (MTT) reduction assay, was found at a much higher dose of chromium(III), (> 50 microM), compared to that of chromium(VI), (> 2.5 microM), in cultured hepatocytes over 20 h treatment at 37 degrees C. Chromium(VI), but not chromium(III), stimulated minimal UDS in hepatocytes at sub-cytotoxic concentrations. A positive UDS response was only observed at cytotoxic concentration. DNA strand breaks in hepatocytes were induced by chromium(VI) following incubation at 37 degrees C for 1 h at doses of 10, 20 and 40 microM sodium dichromate. The subsequent ligation of such strand breaks in hepatocytes treated with 40 microM chromium(VI) for 1 h at 37 degrees C was demonstrated. The majority of strand breaks was repaired within 30 min following removal of the chromate. In conclusion, chromate-induced DNA strand breakage, possibly involving the formation of oxygen radicals and lack of significant UDS have some analogy to those produced by ionizing radiation.
Gao
M
M
Institute of Occupational Health, University of Birmingham, Edgbaston, UK.
Binks
S P
SP
Chipman
J K
JK
Levy
L S
LS
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002857:Chromium / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002857:Chromium; D004247:DNA