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Genotoxicity of azidoalanine in mammalian cells
1Department of Biological Sciences, University of Texas, El Paso 79968.
Abstract:
Sodium azide mutagenesis is mediated through a metabolic intermediate in bacteria and plant species. However, very little is known about the interaction of this intermediate with nucleic acids, its genotoxic potential, or its mechanism of action, especially in mammalian cells. Chinese hamster cells and normal human skin fibroblasts were treated with extracts from Salmonella typhimurium or Hordeum vulgare (barley) containing a crude mutagenic metabolite, as well as with synthetically produced azidoalanine. The cells were evaluated for the induction of sister chromatid exchanges and the ability to perform unscheduled DNA synthesis. With the purified azidoalanine and the azide-treated extracts from Hordeum vulgare, there was a statistically significant increase in the frequency of sister chromatid exchanges observed in both Chinese hamster cells and human fibroblasts. This increase was about twofold, as compared with the control. On the other hand, there was no detectable genotoxic response when cells were exposed to azide-treated extract from Salmonella typhimurium. The results imply that azidoalanine and the crude mutagenic metabolite from Hordeum vulgare are weakly genotoxic in mammalian cells.
Insights
Sodium azide mutagenesis involves a metabolic intermediate. Azidoalanine and barley extracts showed weak genotoxicity in mammalian cells, increasing sister chromatid exchanges.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Sodium azide mutagenesis is linked to a metabolic intermediate.
- The genotoxic potential and mechanism of this intermediate in mammalian cells are poorly understood.
Purpose of the Study:
- To investigate the genotoxicity of a mutagenic metabolite from Hordeum vulgare (barley) and Salmonella typhimurium in mammalian cells.
- To evaluate the effects of azidoalanine on sister chromatid exchanges and unscheduled DNA synthesis.
Main Methods:
- Treatment of Chinese hamster cells and human skin fibroblasts with crude extracts and purified azidoalanine.
- Assessment of sister chromatid exchange (SCE) induction.
- Evaluation of unscheduled DNA synthesis (UDS).
Main Results:
- Purified azidoalanine and Hordeum vulgare extracts significantly increased SCE frequency (approx. twofold) in both cell types.
- No genotoxic response was observed with Salmonella typhimurium extracts.
- Azidoalanine demonstrated weak genotoxicity in mammalian cells.
Conclusions:
- Azidoalanine and the Hordeum vulgare metabolite exhibit weak genotoxic effects in mammalian systems.
- The genotoxic mechanism may involve interaction with nucleic acids, leading to chromosomal aberrations like SCEs.