Chromium-induced production of reactive oxygen species, DNA single-strand breaks, nitric oxide production, and lactate dehydrogenase leakage in J774A.1 cell cultures.
The involvement of oxidative stress in the toxicity of chromium (VI) and chromium (III) has been proposed. We have therefore examined the effects of these cations on the production of superoxide anion, nitric oxide (NO), and DNA single strand breaks (SSB) in J774A.1 macrophage cells in culture as well as the effects on lactate dehydrogenase (LDH) leakage and cell viability. Following a 48 hour incubation, over twofold increases in superoxide anion and NO production were observed at concentrations of approximately 0.30 and 50 microM for Cr (VI) and Cr (III), respectively. The patterns of cell viability and LDH leakage paralleled superoxide anion and NO production for Cr (VI) and Cr (III). A 50% decrease in viability was observed at approximately the concentrations that produced a twofold increase in superoxide and NO production. Concentration-dependent increases in DNA-SSB were observed after incubation with Cr (III) with maximum increases occurring at a concentration of approximately 60 microM. Cr (VI) had no effect on the incidence of DNA-SSB at any of the tested concentrations. The results indicate that Cr (VI) and Cr (III) are toxic to the J774A.1 cell line, and the toxicity may be due at least in part to an oxidative stress induced by the production of reactive oxygen species.
Hassoun
E A
EA
Department of Pharmaceutical and Administrative Sciences, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
Stohs
S J
SJ
D002460:Cell Line; D002712:Chlorides / Q000633:toxicity*; D002840:Chromates / Q000633:toxicity*; D017608:Chromium Compounds / Q000633:toxicity*; D004249:DNA Damage; D007770:L-Lactate Dehydrogenase / Q000032:analysis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002712:Chlorides; D002840:Chromates; D017608:Chromium Compounds; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C016104:sodium bichromate; D007770:L-Lactate Dehydrogenase; C022990:chromic chloride