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Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes

  • Inorganic Compounds
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Abstract

Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0–60 μM), or of nickel subsulfide (Ni3S2) (0–120 μM), or of nickel oxide (NiO) (0–120 μM), or nickel sulfate (NiSO4) (0–120 μM) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 μM but those of Ni3S2 and NiO at 120 μM produced significant increase in the SCE per cell compared to the control value, whereas NiSO4 failed to produce any such significant increase. Except NiSO4, the soluble forms of NiCH, Ni3S2, and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H2O2 scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H2O2, the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca2+]i) movement through plasma membranes), or dantrolene (inhibitor of [Ca2+]i release from sarcoplasmic reticulum), or BAPTA (Ca2+ chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca2+]i is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types of oxidative stress including iron-mediated oxidative stress involving the Fenton–Haber/Weiss reaction, and alterations in calcium homeostasis are involved in the genetic damage produced by the soluble form of NiCH.

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Abbreviations

NiCH:

Nickel carbonate hydroxide

SCE:

Sister-chromatid exchange

RI:

Replication index

MI:

Mitotic index

[Ca2+]i :

Free intracellular calcium level

DFO:

Deferoxamine

SOD:

Superoxide dismutase

DMTU:

Dimethylthiourea

NAC:

N-acetylcysteine

BAPTA:

1,2-bis(2-Aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra-potassium salt

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Acknowledgments

The authors sincerely thank Mrs. Fléchère Fortin for expert technical assistance and the Sainte-Justine Hospital, Montréal for obtaining blood samples from donors.

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Authors and Affiliations

  1. Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Université de Montréal, Main Station, P.O. Box 6128, Montreal, QC, Canada, H3C 3J7

    Prosper M’Bemba-Meka & Saroj K. Chakrabarti

  2. Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Main Station, P.O. Box 6128, Montreal, QC, Canada, H3C 3J7

    Nicole Lemieux

  3. Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, University of Louisville, Louisville, KY, 40292, USA

    Prosper M’Bemba-Meka

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  1. Prosper M’Bemba-Meka
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Correspondence to Prosper M’Bemba-Meka.

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M’Bemba-Meka, P., Lemieux, N. & Chakrabarti, S.K. Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes. Arch Toxicol 81, 89–99 (2007). https://doi.org/10.1007/s00204-006-0128-7

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  • DOI: https://doi.org/10.1007/s00204-006-0128-7

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