Characterization of a nickel resistant mouse cell line
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1Institute of Environmental Medicine, New York University Medical Center, Tuxedo 10987.
Abstract:
Nickel is a potent carcinogen and, at high concentrations, is toxic to mammalian cells. The effects associated with nickel exposure are well-documented but its mechanism of action in the cell has not yet been fully described. In order to understand the metabolic fate of nickel in mammalian cells, a variant cell population has been selected that continues to grow and divide in the presence of nickel chloride concentrations that are toxic to the parental cell line (Balb/c-3T3 mouse fibroblasts). Nickel resistance is not caused by altered uptake of nickel from the medium or increased clearance from the cells and is not associated with changes in metallothionein expression. Compared to the normal cells, the nickel resistant cells have a decreased number of chromosomes and numerous centromeric fusions. The expression of some proteins and the distribution of nickel bound by various proteins are altered in the nickel resistant cells. Preliminary results indicate that the nickel resistant phenotype may be transferred by genomic DNA-mediated transfection into a recipient NIH-3T3 cell line. Current investigations are directed at identifying a gene responsible for nickel resistance.
Insights
Researchers developed nickel-resistant mouse cells to study nickel
Area of Science:
- Cell Biology
- Toxicology
- Genetics
Background:
- Nickel is a known carcinogen and toxic to mammalian cells.
- The precise mechanisms of nickel's cellular action remain unclear.
- Understanding nickel's metabolic fate is crucial for assessing its health risks.
Purpose of the Study:
- To investigate the mechanisms underlying nickel resistance in mammalian cells.
- To characterize the cellular changes associated with acquired nickel resistance.
- To explore the genetic basis of nickel resistance.
Main Methods:
- Selection of a nickel-resistant variant cell line (Balb/c-3T3 mouse fibroblasts).
- Analysis of nickel uptake, clearance, and metallothionein expression.
- Karyotyping to assess chromosomal alterations.
- Protein expression and nickel-binding analysis.
- Genomic DNA-mediated transfection experiments.
Main Results:
- Nickel resistance was not due to altered nickel uptake or clearance, nor metallothionein levels.
- Nickel-resistant cells exhibited reduced chromosome numbers and centromeric fusions.
- Alterations in protein expression and nickel-protein binding were observed.
- The nickel-resistant phenotype showed potential for transfer via DNA transfection.
Conclusions:
- Nickel resistance in mammalian cells involves significant chromosomal alterations.
- The underlying genetic factors responsible for nickel resistance are under investigation.
- This research provides insights into cellular responses to heavy metal toxicity and potential resistance mechanisms.