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Updated: Jan 19, 2026
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
DNA damage in arsenite- and cadmium-treated bovine aortic endothelial cells
Abstract:
Reactive oxygen species have been shown to be involved in the mutagenicity, clastogenicity, and apoptosis of mammalian cells treated with arsenic or cadmium. As these endpoints require several hours of cellular processing, it is not clear that reactive oxygen species damage DNA directly or interfere with DNA replication and repair. Using single-cell alkaline electrophoresis, we have detected DNA strand breaks (DSBs) in bovine aortic endothelial cells by a 4-h treatment with sodium arsenite (As) and cadmium chloride (Cd) in sublethal concentrations. As-induced DSBs could be decreased by nitric oxide (NO) synthase inhibitors, superoxide scavengers, and peroxynitrite scavengers and could be increased by superoxide generators and NO generators. Treatment with As also increased nitrite production. These results suggest that As-increased NO may react with O2*- to produce peroxynitrite and cause DNA damage. The results showing that Cd increased cellular H2O2 levels and that Cd-induced DSBs could be modulated by various oxidant modulators suggest that Cd may induce DSBs via O2*-, H2O2, and *OH. Nevertheless, the DSBs in both As- and Cd-treated cells seem to come from the excision of oxidized bases such as formamidopyrimidine and 8-oxoguanine, as the Escherichia coli enzyme formamidopyrimidine-DNA glycosylase (Fpg) increased DSBs in cells treated with As, 3-morpholinosydnonimine (a peroxynitrite-generating agent), Cd, or H2O2.
Insights
Heavy metals like arsenic and cadmium cause DNA strand breaks in cells. These breaks may result from reactive oxygen species and oxidized base excision, impacting DNA repair mechanisms.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Cellular Biology
Background:
- Reactive oxygen species (ROS) are implicated in DNA damage from arsenic (As) and cadmium (Cd).
- The precise mechanism of ROS-induced DNA damage, whether direct or indirect via replication/repair interference, remains unclear.
Purpose of the Study:
- To investigate the role of reactive oxygen species in DNA strand breaks induced by arsenic and cadmium.
- To elucidate the specific reactive oxygen species and pathways involved in metal-induced DNA damage.
Main Methods:
- Single-cell alkaline electrophoresis was used to detect DNA strand breaks (DSBs).
- Bovine aortic endothelial cells were treated with sublethal concentrations of sodium arsenite and cadmium chloride.
- Modulation of DSBs was assessed using various oxidant/antioxidant agents, nitric oxide (NO) synthase inhibitors, and superoxide/peroxynitrite scavengers.
- The effect of Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) on DSBs was evaluated.
Main Results:
- Both arsenic and cadmium induced significant DNA strand breaks in endothelial cells within 4 hours.
- Arsenic-induced DSBs were linked to increased nitric oxide production and potentially peroxynitrite formation.
- Cadmium-induced DSBs were associated with increased hydrogen peroxide (H2O2) and likely involved superoxide (O2*-) and hydroxyl radical (*OH).
- The enzyme Fpg enhanced DSBs in cells treated with arsenic, cadmium, peroxynitrite generators, or H2O2, suggesting oxidized base excision.
Conclusions:
- Arsenic and cadmium induce DNA strand breaks in endothelial cells through distinct reactive oxygen species-mediated pathways.
- Nitric oxide and peroxynitrite are implicated in arsenic-induced DNA damage.
- Superoxide, hydrogen peroxide, and hydroxyl radical are likely involved in cadmium-induced DNA damage.
- DNA strand breaks in metal-treated cells may arise from the excision of oxidized DNA bases.
