Influence of reducing compounds on the formation of DNA-protein cross-links in HL-60 cells induced by hexavalent chromium.
The influence of reducing compounds on the formation of DNA--protein cross-links induced by hexavalent chromium was studied in the human cell line HL-60. Analysis of cytoplasmic concentration of ascorbic acid and glutathione by HPLC in these cells showed that ascorbic acid was not detectable (detection limit: 0.1 nmol). The cellular content of glutathione was low (6 nmol/million cells). It could easily be depleted with diethylmaleate. The effect of glutathione, ascorbic acid and ascorbyl palmitate alone, or glutathione in combination with ascorbyl palmitate was investigated. It could be shown that glutathione increased DNA--protein cross-links in HL-60 cells by chromate significantly in a dose dependent manner, while pre-incubation with L-ascorbic acid and L-ascorbic acid-6-hexadecanate (ascorbyl palmitate) did not change the cross-linking activity of chromate significantly. Ascorbyl palmitate counteracted the increasing effect of glutathione on the concentration of DNA--protein cross-links in HL-60 cells after exposure to chromate. As ascorbic acid reacts much faster with hexavalent chromium at physiological pH than glutathione does, this suggests an influence of the reaction velocity of the redox reaction between hexavalent chromium and the reducing compounds on the toxification of Cr(VI) and formation of DNA--protein cross-links.
Capellmann
M
M
National Institute of Public Health, Department of Environmental Medicine, Oslo, Norway.
Mikalsen
A
A
Hindrum
M
M
Alexander
J
J
D016587:Antimutagenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002840:Chromates / Q000378:metabolism; D002857:Chromium / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008298:Maleates / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D016587:Antimutagenic Agents; D002274:Carcinogens, Environmental; D002840:Chromates; D004273:DNA, Neoplasm; D008298:Maleates; D009363:Neoplasm Proteins; D002857:Chromium; C074702:chromium hexavalent ion; C014476:diethyl maleate; D005978:Glutathione; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid