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DNA-protein cross-links induced by nickel compounds in intact cultured mammalian cells
Abstract:
The carcinogenic activity of crystalline NiS has been attributed to phagocytosis and intracellular dissolution of the particles to yield Ni2+ which is thought to enter the nucleus and damage DNA. In this study the extent and type of DNA damage in Chinese hamster ovary CHO cells treated with various nickel compounds was assessed by alkaline elution. Both insoluble (crystalline NiS) and soluble (NiCl2) nickel compounds induced single strand breaks and DNA protein cross-links. The single strand breaks were repaired relatively quickly but the DNA-protein cross-links were present and still accumulating 24 h after exposure to nickel. Single strand breakage occurred at both non-cytotoxic and cytotoxic concentrations of nickel, however, DNA-protein cross-linking was absent when cells were exposed to toxic nickel levels. The concentration of nickel that induced DNA-protein cross-linking correlated with those metal concentrations that reversibly inhibited cellular replication.
Insights
Nickel compounds cause DNA damage, including single-strand breaks and DNA-protein cross-links, in Chinese hamster ovary (CHO) cells. DNA-protein cross-links accumulate over time and correlate with inhibited cell replication.
Area of Science:
- Toxicology
- Molecular Biology
- Environmental Health
Background:
- Crystalline nickel sulfide (NiS) carcinogenicity is linked to intracellular nickel ion (Ni2+) release and subsequent DNA damage.
- Understanding nickel-induced genotoxicity is crucial for assessing health risks associated with nickel exposure.
Purpose of the Study:
- To investigate the types and extent of DNA damage induced by various nickel compounds in Chinese hamster ovary (CHO) cells.
- To elucidate the relationship between nickel exposure levels, DNA damage, and cellular replication.
Main Methods:
- Alkaline elution assay was used to assess DNA single-strand breaks and DNA-protein cross-links.
- Chinese hamster ovary (CHO) cells were treated with different nickel compounds, including crystalline NiS and NiCl2.
- Cellular replication was monitored to assess cytotoxicity.
Main Results:
- Both insoluble crystalline NiS and soluble NiCl2 induced DNA single-strand breaks and DNA-protein cross-links in CHO cells.
- DNA single-strand breaks were repaired rapidly, while DNA-protein cross-links persisted and accumulated up to 24 hours post-exposure.
- DNA-protein cross-linking occurred at non-cytotoxic nickel concentrations, but was absent at toxic levels.
- Nickel concentrations inducing DNA-protein cross-linking correlated with reversible inhibition of cellular replication.
Conclusions:
- Nickel compounds induce distinct types of DNA damage, including persistent DNA-protein cross-links.
- DNA-protein cross-linking is a sensitive indicator of nickel genotoxicity and may be linked to nickel-induced replication inhibition.
- These findings contribute to understanding the molecular mechanisms of nickel carcinogenicity.