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Related Experiment Videos

Salmonella/human S9 mutagenicity test: a collaborative study with 58 compounds.

Atsushi Hakura1, Hiroyasu Shimada, Madoka Nakajima

  • 1Drug Safety Research Laboratories, Eisai Co., Ltd, 1 Takehaya-machi, Kawashima-cho, Hashima-gun, Gifu 501-6195, Japan. a-hakura@hhc.eisai.co.jp

Mutagenesis
|April 22, 2005
PubMed
Summary

Human liver S9 fractions in the Salmonella mutagenicity test (Ames test) show varied chemical mutagenicity compared to rat S9 fractions. This study highlights inter-individual diversity, suggesting human S9 fractions improve understanding of human chemical mutagenic effects.

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Area of Science:

  • Toxicology and Pharmacology
  • Genetics and Molecular Biology

Background:

  • The Salmonella mutagenicity test (Ames test) is a standard for assessing chemical mutagenicity.
  • Rat liver S9 fractions are commonly used, but human relevance is a concern.
  • Human liver S9 fractions offer a more direct model for human metabolism and toxicity.

Purpose of the Study:

  • To evaluate the performance of human liver S9 fractions in the Ames test.
  • To compare mutagenicity of chemicals using human versus rat liver S9 fractions.
  • To investigate inter-individual variability in mutagenic responses with human S9 fractions.

Main Methods:

  • A collaborative study involving JEMS/BMS and HAB assessed 58 chemicals using the Ames test.
  • Mutagenicity was determined using Salmonella typhimurium strains (TA100, TA98, YG7108).

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  • Tests were conducted with high-activity human liver S9, pooled human liver S9, and standard rat liver S9 fractions.

    • Main Results:

    • Mutagenicity varied significantly between human and rat liver S9 fractions depending on the chemical.
    • Human S9 fractions revealed substantial inter-individual diversity in mutagenic responses.
    • 75% of mutagens were less potent with human S9 fractions, while 25% (e.g., aromatic amines) were more potent.

    Conclusions:

    • Human liver S9 fractions provide a more relevant assessment of chemical mutagenicity for humans.
    • The observed inter-individual diversity underscores the importance of using human-derived systems.
    • Incorporating human S9 fractions in mutagenicity testing can enhance the understanding of human health risks.