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Mutagenicity of nitroxyl compounds: structure-activity relationships
B Gallez1, C De Meester, R Debuyst
1Department of Pharmaceutical Sciences, Catholic University of Louvain, Brussels, Belgium.
Toxicology Letters
|October 1, 1992
Summary
Three piperidinoxyl radicals showed direct mutagenicity in Salmonella typhimurium TA 100. Their mutagenic activity, linked to free radical nature, was reduced by ascorbic acid and rat liver fractions.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- Nitroxyl spin labels are used in various biological studies.
- The mutagenicity of nitroxyl compounds requires further investigation.
Purpose of the Study:
- To assess the mutagenic potential of piperidinoxyl and pyrrolidinoxyl compounds.
- To investigate the relationship between the free radical nature of these compounds and their mutagenicity.
Main Methods:
- Bacterial mutagenicity testing using Salmonella typhimurium strains TA 100, TA 98, and TA 102.
- In vitro assays involving partial reduction with ascorbic acid.
- Incubation with cofactor-supplemented rat liver subcellular fractions.
Main Results:
- Three piperidinoxyl radicals were directly mutagenic in Salmonella typhimurium TA 100.
- One pyrrolidinoxyl compound exhibited weaker mutagenic activity; two others were inactive.
- Mutagenicity was abolished by ascorbic acid reduction, indicating a link to the free radical state.
- Mutagenic activity was reduced by rat liver fractions.
- Higher mutagenicity correlated with greater resistance of nitroxyl spin labels to reduction.
Conclusions:
- Piperidinoxyl radicals can be directly mutagenic.
- The mutagenicity of these nitroxyl compounds is associated with their free radical properties.
- Metabolic activation or detoxification may occur in the presence of liver fractions.