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Dimethylated arsenics induce DNA strand breaks in lung via the production of active oxygen in mice
K Yamanaka1, A Hasegawa, R Sawamura
1Department of Pharmacy, Nihon University College of Science and Technology, Tokyo, Japan.
Abstract:
In order to study the genotoxicity of arsenics, we focused our attention on dimethylarsinic acid (DMAA) which was a main metabolite of inorganic arsenics in mammals. ICR mice were orally administered DMAA-Na (1500mg/kg). DNA single-strand breaks occurred specifically in lung at 12h after administration. An in vitro experiment indicated that the breaks were not caused directly by DMAA but by dimethylarsine, a further metabolite of DMAA. Furthermore, the dimethylarsine-induced breaks were diminished by the addition of SOD and catalase, suggesting that active oxygen produced by dimethylarsine was involved in the induction of DNA damage.
Insights
Dimethylarsinic acid (DMAA), a key arsenic metabolite, causes DNA damage in mouse lungs. This genotoxicity is mediated by a further metabolite, dimethylarsine, and involves active oxygen species.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Biochemistry
Background:
- Arsenic compounds are environmental toxins with known genotoxic effects.
- Dimethylarsinic acid (DMAA) is a primary mammalian metabolite of inorganic arsenic.
- Understanding the genotoxicity of DMAA is crucial for assessing arsenic health risks.
Purpose of the Study:
- To investigate the genotoxicity of dimethylarsinic acid (DMAA).
- To identify the specific arsenic metabolite responsible for DNA damage.
- To elucidate the mechanism underlying DMAA-induced DNA damage.
Main Methods:
- Oral administration of DMAA-Na to ICR mice.
- Analysis of DNA single-strand breaks in mouse lung tissue.
- In vitro experiments to assess direct DMAA effects and metabolite activity.
- Evaluation of the role of active oxygen species using SOD and catalase.
Main Results:
- DMAA administration induced DNA single-strand breaks specifically in mouse lungs 12 hours post-administration.
- In vitro studies revealed DMAA itself did not directly cause breaks; a further metabolite, dimethylarsine, was responsible.
- Dimethylarsine-induced DNA breaks were reduced by superoxide dismutase (SOD) and catalase.
- These findings implicate active oxygen species in the genotoxic mechanism.
Conclusions:
- Dimethylarsinic acid (DMAA) is a genotoxic agent in vivo, primarily affecting lung tissue.
- The genotoxicity of DMAA is mediated by its metabolite, dimethylarsine.
- Dimethylarsine induces DNA damage through the production of active oxygen species, highlighting a critical pathway in arsenic toxicity.