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Structure-mutagenicity relationships of benzidine analogues.

E A Messerly1, J E Fekete, D R Wade

  • 1College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.

Environmental and Molecular Mutagenesis
|January 1, 1987
PubMed
Summary
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Benzidine analogues were tested for mutagenicity using the Ames test. Mutagenic activity, particularly with rat liver S9 activation, varied significantly among compounds, with dichlorobenzidine and 4-aminobiphenyl showing high potency.

Area of Science:

  • Toxicology
  • Genetics
  • Chemical Mutagenesis

Background:

  • Benzidine and its analogues are known environmental contaminants.
  • Assessing their mutagenic potential is crucial for understanding their health risks.

Purpose of the Study:

  • To compare the mutagenic activities of benzidine, its dihydrochloride salt, and twelve analogues.
  • To evaluate the influence of structural modifications and metabolic activation on mutagenicity.

Main Methods:

  • The Ames test was employed using bacterial strains TA100 and TA98.
  • Tests were conducted with and without rat liver S9 fraction to assess metabolic activation.

Main Results:

  • Most compounds showed little to no mutagenicity without S9 activation.

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  • With S9 activation, all compounds except tetramethylbenzidine were active in TA100; dichlorobenzidine and 4-aminobiphenyl were most potent.
  • Bridged diphenyl compounds were less mutagenic in TA98 than planar biphenyls, except for a nitroaniline derivative which was mutagenic in both strains, with or without S9.
  • Conclusions:

    • Mutagenicity of benzidine analogues is structure-dependent and often requires metabolic activation.
    • A decrease in the basicity of parent anilines correlated with increased mutagenicity for certain 3,3'-disubstituted benzidines.