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Carcinogenesis

Altered Oxidative Stress Responses in Nickel-resistant Mammalian Cells

Konstantin Salnikow, Min Gao, Vika Voitkun, Xi Huang and Max Costa
Konstantin Salnikow
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Min Gao
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Vika Voitkun
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Xi Huang
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Max Costa
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DOI:  Published December 1994
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Abstract

BALB 3T3 cells exposed to NiCl2 acquired resistance to concentrations as high as 200 µm and retain resistance for many generations in the absence of nickel. This resistance was not due to alterations in uptake or to metallothionein overexpression. The nickel-resistant B200 cell line was found to also exhibit cross-resistance to hydrogen peroxide and menadione. These nickel-resistant cells had 1.8 times higher basal levels of glutathione compared to wild-type cells. Studies with the glutathione synthesis inhibitor buthionine sulfoximine showed that while glutathione turnover was more rapid in the nickel-resistant cells, its depletion following NiCl2 treatment of the parental BALB 3T3 cell line was greater than in the nickel-resistant B200 cells. The reduced level of binding of NFkB and AP-1 transcription factors to their DNA consensus sequences in B200 cells compared to wild-type cells, and their more reactive response following treatment of resistant cells with H2O2 or buthionine sulfoximine, strengthens the hypothesis that nickel resistance is closely allied to oxidative stress responses.

Footnotes

  • ↵1 This work was supported from NIH Grants ES 00260, ES 04895, ES 04715, and ES 05512, and National Cancer Institute Grant CA 16087.

  • ↵2 To whom all requests for reprints should be addressed, at Nelson Institute of Environmental Medicine and The Kaplan Comprehensive Cancer Center, New York University Medical Center, 550 First Avenue, New York, NY 10016.

  • Received August 4, 1994.
  • Accepted October 19, 1994.
  • ©1994 American Association for Cancer Research.
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December 1994
Volume 54, Issue 24
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Altered Oxidative Stress Responses in Nickel-resistant Mammalian Cells
Konstantin Salnikow, Min Gao, Vika Voitkun, Xi Huang and Max Costa
Cancer Res December 15 1994 (54) (24) 6407-6412;

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Altered Oxidative Stress Responses in Nickel-resistant Mammalian Cells
Konstantin Salnikow, Min Gao, Vika Voitkun, Xi Huang and Max Costa
Cancer Res December 15 1994 (54) (24) 6407-6412;
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