PROTECTIVE EFFECT OF DEFEROXAMINE ON CHROMIUM(VI)-INDUCED DNA SINGLE-STRAND BREAKS, CYTOTOXICITY, AND LIPID-PEROXIDATION IN PRIMARY CULTURES OF RAT HEPATOCYTES

Incubation of primary cultures of rat hepatocytes with K2Cr2O7 and def eroxamine (DFO), an iron chelator, resulted in a marked decrease in ce llular levels of DNA single-strand breaks caused by K2Cr2O7 Cellular t reatment with DFO also suppressed both dichromate-induced cytotoxicity - evaluated by the leakage of lactate dehydrogenase, and lipid peroxi dation - as monitored by malondialdehyde formation. In addition, treat ment with DFO attenuated the suppression of the levels of vitamin E an d C as well as the inhibition of alkaline phosphatase and glutathione peroxidase activity attributed to K2Cr2O7 However, DFO had no influenc e on the cellular level of glutathione or the activity of glutathione reductase and superoxide dismutase suppressed by dichromate. Under the same experimental conditions, cellular uptake and distribution of chr omium were not affected by DFO. These results indicate that DFO protec ts cells from chromium(VI)-induced DNA strand breaks, cytotoxicity, li pid peroxidation, vitamin E and C depression, and glutathione peroxida se inhibition. The role of antioxidants in chromium(VI)-induced cytoto xicity, DNA breaks, and lipid peroxidation is discussed.