Nickel(II) affects poly(ADP-ribose) polymerase-mediated DNA repair in normal and cancer cells

Area of Science:

• Biochemistry
• Genotoxicology
• Molecular Biology

Background:

• Nickel(II) is known to be genotoxic, but the precise mechanisms remain unclear.
• DNA repair pathways are potential targets for nickel-induced genotoxicity.
• Poly(ADP-ribose) polymerase (PARP) plays a crucial role in DNA repair.

Purpose of the Study:

• To investigate the effect of nickel chloride on DNA repair.
• To examine the impact of nickel chloride on PARP-mediated DNA repair following gamma-radiation and idarubicin exposure.
• To explore nickel(II)'s potential interference with DNA repair independent of PARP.

Main Methods:

• Utilized the alkaline comet assay to assess DNA damage and repair.
• Employed normal and cancer cell lines for experiments.
• Exposed cells to gamma-radiation and idarubicin to induce DNA damage.
• Administered nickel chloride at a non-cytotoxic concentration (1 microM).

Main Results:

• Nickel chloride at 1 microM significantly affected PARP-mediated DNA repair.
• The genotoxic effects were observed for DNA lesions induced by both idarubicin and gamma-radiation.
• In quiescent lymphocytes, nickel(II) appeared to interfere with DNA repair independently of PARP.

Conclusions:

• Nickel(II) can interfere with DNA repair processes at non-cytotoxic concentrations.
• PARP-mediated DNA repair is a sensitive target for nickel(II).
• Nickel(II) may also impact DNA repair through PARP-independent pathways.