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A possible role for chromium(III) in genotoxicity.
1Department of Environmental Medicine, New York University Medical Center, A.J. Lanza Laboratory, Tuxedo 10987.
Environmental Health Perspectives
|May 1, 1991
Summary
Chromium (CrIII) increases DNA replication rates and decreases fidelity, leading to mutations. This suggests CrIII contributes to chromium-induced genotoxicity and cancer.
Area of Science:
- Environmental Science
- Toxicology
- Molecular Biology
Background:
- Chromium exists as CrIII and CrVI; CrVI is biologically active, reducing to CrIII intracellularly.
- CrIII is abundant, less permeable, but can be genotoxic by interacting with DNA and proteins.
- The genotoxicity of CrIII requires further investigation.
Purpose of the Study:
- To investigate the genotoxicity of CrIII.
- To determine if CrIII affects DNA replication and fidelity.
- To explore CrIII's role in chromium-mediated carcinogenesis.
Main Methods:
- In vitro DNA replication assay using purified DNA polymerases and a CrIII-treated DNA template.
- In vivo genotoxicity assessment via CaCl2-mediated transfection of CrIII-treated DNA into Escherichia coli.
- Quantification of DNA replication rate, polymerase processivity, and mutation frequency.
Main Results:
- CrIII significantly increased DNA replication rate and polymerase processivity in vitro.
- CrIII-treated DNA induced a dose-dependent increase in mutation frequency in E. coli.
- CrIII alters DNA-polymerase interactions, reducing replication fidelity.
Conclusions:
- CrIII enhances DNA replication and reduces its accuracy.
- These alterations in DNA replication contribute to CrIII mutagenicity.
- CrIII is implicated as a factor in chromium-induced carcinogenesis.