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Endogenous mutagens derived from amino acids.

H Glatt1

  • 1Department of Toxicology, University of Mainz, F.R.G.

Mutation Research
|May 1, 1990
PubMed
Summary

L-Cysteine and N-acetyl-L-cysteine showed mutagenic effects in bacterial tests. However, in mammalian cells, only homogentisic acid demonstrated significant mutagenicity, particularly in alkaptonuria patients.

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Area of Science:

  • Biochemistry
  • Toxicology
  • Genetics

Background:

  • L-Cysteine and its precursor N-acetyl-L-cysteine are widely used supplements.
  • Tyrosine metabolites like levodopa and homogentisic acid are relevant in metabolic pathways.
  • Alkaptonuria is a genetic disorder characterized by elevated homogentisic acid levels.

Purpose of the Study:

  • To investigate the mutagenic potential of L-cysteine, glutathione, N-acetyl-L-cysteine, levodopa, and homogentisic acid.
  • To compare mutagenicity in bacterial and mammalian cell systems.
  • To assess the implications of homogentisic acid's mutagenicity in alkaptonuria.

Main Methods:

  • Bacterial mutagenicity assays using Salmonella typhimurium strains (TA97, TA92, TA104) with kidney preparations.
  • Mammalian cell gene mutation assays in V79 Chinese hamster cells measuring resistance to 6-thioguanine.
  • Comparative analysis of mutagenic effects across different cell systems and compounds.

Main Results:

  • L-Cysteine, glutathione, and N-acetyl-L-cysteine induced mutagenicity in Salmonella typhimurium.
  • Levodopa and homogentisic acid also showed mutagenic effects in bacteria, though weaker.
  • In V79 cells, L-cysteine and N-acetyl-L-cysteine were inactive, levodopa was weakly mutagenic, and homogentisic acid was strongly mutagenic (135-fold increase).

Conclusions:

  • Homogentisic acid exhibits significant mutagenic potential in mammalian cells, with implications for alkaptonuria.
  • The mutagenicity of these compounds varies significantly between bacterial and mammalian test systems.
  • Further research is warranted on the genotoxic effects of amino acids and metabolites.

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