Evaluation of oxidative damage and inhibition of DNA repair in an in vitro study of nickel exposure.
It has been suggested that Nickel is involved in oxidative damage and inhibition of DNA repair. We studied the effects of NiSO4 on oxidative stress and DNA repair in Jurkat cells to elucidate its mechanism of action. Cells were treated with H2O2 and ROS generation (by flow cytometry), and oxidative DNA damage (as tail moment by Fpg-enzyme comet test), were evaluated immediately and after 4 and 24 h of DNA damage recovery occurred in presence or absence of NiSO4 (0.017 and 0.17 microM) to clarify possible interactions of Ni with DNA repair processes. Moreover, cells were exposed to the same doses of NiSO4 for 4 and 24 hours to evaluate its direct oxidative effect. The results of the comet test showed high tail moment immediately after oxidative burst with a decreasing after 4 h of DNA recovery, and a slight increase after 24 h of recovery. The decreases were more limited for cells treated with NiSO4 0.17 microM indicating an inhibition of oxidative DNA damage repair by this substance. An induction of ROS was observed after 4 h of incubation with higher dose of NiSO4. Cells treated with H2O2 showed the highest level of ROS after 4 h of recovery in presence of NiSO4 0.17 microM that remained at elevated levels also after 24 h of recovery suggesting a synergistic action of Ni with H2O2 in the reduction of cellular anti-oxidative defence activities.
Cavallo
D
D
Department of Occupational Health, ISPESL National Institute for Occupational Safety and Prevention, Via Fontana Candida, 1-00040 Monteporzio Catone, Rome, Italy. cavallo.d@tiscali.it
Ursini
C L
CL
Setini
A
A
Chianese
C
C
Piegari
P
P
Perniconi
B
B
Iavicoli
S
S
D002273:Carcinogens / Q000633:toxicity*; D020552:Comet Assay; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D002273:Carcinogens; D017382:Reactive Oxygen Species; D009532:Nickel; D006861:Hydrogen Peroxide