DNA damage in human colonic mucosa cells evoked by nickel and protective action of quercetin - involvement of free radicals?
Nickel is a toxic and carcinogenic environmental and occupational pollutant and quercetin is a dietary flavonoid that is reported to modulate effects of many mutagens and carcinogens. We investigated the ability of nickel chloride to induce DNA damage in human colonic mucosa cells in the presence of quercetin, using the alkaline comet assay. Nickel chloride (5-250 micromol/L) evoked dose-dependent DNA damage and quercetin at 50 micromol/L decreased the extent of this damage. The cells exposed to nickel chloride progressively removed their DNA damage and the presence of 50 micromol/L quercetin in the repair-incubation medium did not affect the repair kinetics. Cells exposed to nickel and treated with endonuclease III, an enzyme recognizing oxidized bases, displayed a greater extent of DNA damage than those not treated with the enzyme. Quercetin did not exert a significant effect on the production of oxidized bases by nickel. Pretreatment of the cells with a nitrone spin trap, N-tert-butyl-alpha-phenylnitrone, decreased the extent of DNA damage evoked by nickel. Quercetin caused a further decrease in the extent of the damage in the presence of the trap. The results obtained suggest that reactive oxygen species, including free radicals, might be involved in the formation of DNA lesions induced by nickel chloride in colonic mucosa cells and that quercetin may exert protective effects in these cells.
Department of Molecular Genetics, University of Lodz, Poland. januszb@biol.uni.lodz.pl
J
J
Błasiak
M
M
Arabski
T
T
Pertyński
E
E
Małecka-Panas
K
K
Woźniak
J
J
Drzewoski
D002460:Cell Line; D002470:Cell Survival; D003106:Colon / Q000187:drug effects*; D020552:Comet Assay; D003497:Cyclic N-Oxides; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D007700:Kinetics; D008956:Models, Chemical; D009532:Nickel / Q000494:pharmacology / Q000633:toxicity*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D013997:Time Factors
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; C022838:nickel chloride; D009532:Nickel; D011794:Quercetin; D010100:Oxygen