Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogen aniline is negative in the Ames Salmonella mutagenicity assay. Aniline does, however, induce intrachromosomal recombination between repeated sequences in Saccharomyces cerevisiae, resulting in deletion (DEL) of intervening sequences. We have investigated whether the generation of oxidative free radical species by aniline and/ or its metabolites may be responsible for its recombinagenic activity in yeast. The toxicity and recombinagenicity of aniline in yeast were greatly reduced in the presence of the free radical scavenger N-acetyl cysteine. Aniline cytotoxicity was many-fold increased in strains of S.cerevisiae lacking the antioxidant enzyme superoxide dismutase. Aniline also induced oxidation of the intracellular free radical-sensitive reporter compound 2,4-dichlorofluorescin diacetate to its fluorescent derivative 2,4-dichlorofluorescein in vivo in S.cerevisiae. The aniline metabolites 4-aminophenol and 2-aminophenol were significantly more potent inducers of DEL recombination in yeast than aniline. In contrast, the secondary metabolite 4-acetamidophenol (acetaminophen) was non-toxic and non-recombinagenic in yeast. 4-Aminophenol and 2-aminophenol were also significantly more toxic than aniline in a superoxide dismutase deficient yeast strain. 4-aminophenol was a significantly more potent oxidizer of 2,4-dichlorofluorescin diacetate than aniline. The Escherichia coli soxS promoter, which is induced in the presence of redox cycling agents like paraquat, was induced weakly by aniline at toxic doses. The soxS promoter was strongly induced by 4-aminophenol and 2-aminophenol. The results indicate a role for oxidative stress, mediated by generation of superoxide radical, in the toxicity and recombinagenicity of aniline. The increased activity of 4-aminophenol and 2-aminophenol suggests that ring hydroxylation may be an important activating step in this process.
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PMID:Aniline and its metabolites generate free radicals in yeast. 923 64