Skip NavigationSkip to Content
Return Return to Search Results

Mechanisms of arsenic-induced cross-tolerance to nickel cytotoxicity, genotoxicity, and apoptosis in rat liver epithelial cells

  1. Author:
    Qu, W.
    Kasprzak, K. S.
    Kadiiska, M.
    Liu, J.
    Chen, H.
    Maciag, A.
    Mason, R. P.
    Waalkes, M. P.

  2. Author Address

    NIEHS, NCI, Chief Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, POB 12233, Mail Drop F0-09, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NIEHS, NCI, Chief Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI, Met Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Waalkes MP NIEHS, NCI, Chief Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, POB 12233, Mail Drop F0-09, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
    1. Year: 2001
  2. Journal: Toxicological Sciences
    1. 63
    2. 2
    3. Pages: 189-195
  4. Type of Article: Article
  1. Abstract:

    The purpose of the present study was to investigate the mechanism of cross-tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE) cells (TRL 1215 cells, which had been continuously exposed to 0.5 muM arsenite for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for 24 h, and cell viability was determined by metabolic integrity. The LC50 for nickel was 608 +/- 32 muM in CAsE cells as compared to 232 +/- 16 muM in control cells, a 2.6-fold increase. CAsE and control cells were treated with 200 muM nickel for 4 h and cellular-free radical production was measured using ESR spectrometry. Hydroxyl radical generation was decreased in CAsE cells. Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8-oxo-2'- deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells lost their nickel resistance. The mechanism of arsenic-induced cross- tolerance to cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a generalized resistance to oxidant-induced injury, probably based, at least in part, in increased cellular GSH levels.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel