Related Experiment Video
Updated: Aug 8, 2026
Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
Published on: June 9, 2020
Inhibition by metals of X-ray and ultraviolet-induced DNA repair in human cells
R D Snyder1, G F Davis, P J Lachmann
1Merrell Dow Research Institute, Cincinnati, OH 45215.
Abstract:
A number of metals have been shown to be involved in the etiology of animal and human neoplasms. The molecular mechanisms have not yet been determined, but the observed plethora of genetic effects observed following treatment of mammalian cells with metals clearly indicates the possibility that metals can exert their effects at least partially at the level of DNA metabolism. Several studies have suggested that metal treatment may inhibit normal DNA repair processes in procaryotic and eucaryotic cells but a systematic study of this question has not previously been conducted. The present study surveyed the ability of 15 metal salts to interfere with repair of X-ray or UV-induced DNA damage in HeLa cells. Hg+(+), As++(+), Cu+(+), Ni+(+), Co+(+), and Cd+(+) were shown to inhibit the excision of pyrimidine dimers from DNA and to do so in a dose-dependent fashion. Inhibition of repair by only Ni+(+) and Co+(+) resulted in the accumulation of long-lived DNA strand breaks suggestive of a block in the gap-filling stage of repair. Ability to inhibit repair was not correlated with cytotoxicity. X-ray repair was sensitive to Hg+(+), Ni+(+), As++(+), Ga+(+), Zn+(+), and Mo(VI). All inhibitory metals inhibited closure of single strand DNA breaks. Ga+(+) appeared, in addition, to inhibit a later step involving chromatin reconstitution. These findings support the notion that interference of DNA repair processes may be a consequence of exposure of mammalian cells to certain metals. This may be a factor in the etiology of metal-associated carcinogenesis.
Insights
Certain metals, including mercury and arsenic, can interfere with DNA repair mechanisms in human cells. This disruption of DNA repair may contribute to metal-induced cancer development.
Area of Science:
- Environmental toxicology
- Molecular biology
- Carcinogenesis
Background:
- Metals are implicated in the development of neoplasms.
- Metals may affect DNA metabolism and repair processes.
- Previous studies suggest metal-induced inhibition of DNA repair, but a systematic investigation is lacking.
Purpose of the Study:
- To systematically investigate the ability of various metal salts to interfere with DNA repair in mammalian cells.
- To identify specific metals that inhibit DNA repair pathways.
- To explore the potential link between metal-induced DNA repair inhibition and carcinogenesis.
Main Methods:
- Surveyed 15 metal salts for their effects on DNA repair in HeLa cells.
- Assessed interference with repair of X-ray or UV-induced DNA damage, including pyrimidine dimer excision and strand break repair.
- Examined dose-dependent inhibition and effects on specific repair stages.
Main Results:
- Mercury (Hg+), arsenic (As++), copper (Cu+), nickel (Ni+), cobalt (Co+), and cadmium (Cd+) inhibited pyrimidine dimer excision in a dose-dependent manner.
- Nickel (Ni+) and cobalt (Co+) caused accumulation of DNA strand breaks, suggesting a block in repair.
- Several metals (Hg+, Ni+, As++, Ga+, Zn+, Mo(VI)) interfered with X-ray repair, and all inhibited single-strand break repair closure.
Conclusions:
- Metal exposure can interfere with crucial DNA repair processes in mammalian cells.
- Inhibition of DNA repair by metals like mercury, arsenic, and nickel may be a mechanism underlying metal-associated carcinogenesis.
- These findings highlight the genotoxic potential of certain metals and their role in cancer etiology.
Related Concept Videos
01:08Nucleotide Excision Repair
02:25Overview of DNA Repair
Chemically...
02:36DNA Damage can Stall the Cell Cycle
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:18Other Unique Bacteria