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Strand breakage and decreased molecular weight of DNA induced by specific metal compounds
Abstract:
The effect of various metal compounds on the DNA of Chinese hamster ovary (CHO) cells was studied. Both NiCl2 and crystalline NiS caused DNA strand breaks in cultured CHO cells, whereas amorphous NiS did not. Strand breaks were quantitated by determining the number of average molecular weight of DNA following treatment with the metal compounds. Exposure of cells to crystalline NiS, CoS, CdS, AgS, CuS and Ni3S2 at 10 micrograms/ml for 24 h also induced DNA strand breaks. Similar exposure to activated charcoal, which was also actively phagocytosed, failed to cause any effect on the DNA of CHO cells. In the case of NiCl2 and NiS the effect was shown to be both time and dose dependent. Other soluble metal compounds such as HgCl2, CaCrO4, and CdCl2 also decreased the molecular weight of DNA while MnCl2, ZnCl2 and FeCl2 caused no significantly detectable change in DNA molecular weight. These effects, which occur at low metal concentrations suggest that nickel and other metals which cause cellular transformation have a very selective and specific effect upon DNA.
Insights
Certain nickel compounds and other metals cause DNA strand breaks in Chinese hamster ovary (CHO) cells. These metal-induced DNA alterations suggest a selective effect on DNA, potentially linked to cellular transformation.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Metal compounds are known to interact with biological systems.
- Understanding the genotoxicity of metals is crucial for risk assessment.
- Chinese hamster ovary (CHO) cells are a standard model for genotoxicity testing.
Purpose of the Study:
- To investigate the effects of various metal compounds on DNA integrity in CHO cells.
- To determine the dose and time dependency of metal-induced DNA damage.
- To explore the relationship between metal-induced DNA damage and cellular transformation.
Main Methods:
- Treatment of cultured CHO cells with different metal compounds (e.g., NiCl2, NiS, CoS, CdS, HgCl2).
- Quantitation of DNA strand breaks by measuring the average molecular weight of DNA.
- Assessment of dose and time dependency for specific metal exposures.
Main Results:
- Crystalline NiS, NiCl2, CoS, CdS, AgS, CuS, Ni3S2, HgCl2, CaCrO4, and CdCl2 induced DNA strand breaks or decreased DNA molecular weight.
- Amorphous NiS, activated charcoal, MnCl2, ZnCl2, and FeCl2 did not cause significant DNA damage.
- The effects of NiCl2 and NiS were found to be both time and dose-dependent.
Conclusions:
- Nickel compounds, particularly crystalline NiS and NiCl2, are genotoxic to CHO cells, causing DNA strand breaks.
- Several other metal compounds also exhibit genotoxic effects, impacting DNA integrity.
- The observed DNA damage at low concentrations suggests a selective and specific mechanism for metals implicated in cellular transformation.