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Initial experiences and future directions for transgenic mouse mutation assays

T Suzuki1, M Hayashi, T Sofuni

  • 1Division of Genetics and Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.

Mutation Research
|June 1, 1994
PubMed
Summary
This summary is machine-generated.

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This study combined micronucleus and gene mutation assays in transgenic mice to detect genotoxicity. The combined approach successfully identified mutagenic effects, showing tissue-specific responses for safety testing.

Area of Science:

  • Toxicology
  • Genetics
  • Biotechnology

Background:

  • Transgenic mice offer novel approaches for mutation research and safety testing.
  • The lacZ transgenic mouse (Muta Mouse) model allows for in vivo mutation detection.

Purpose of the Study:

  • To combine the peripheral blood micronucleus assay with the transgenic mouse mutation assay for simultaneous detection of gene mutations and micronucleus induction.
  • To evaluate the efficacy of this combined assay in detecting genotoxicity of known mutagens.

Main Methods:

  • Utilized lacZ transgenic mice (Muta Mouse) for combined in vivo testing.
  • Administered mutagens: mitomycin C (MMC), ethyl nitrosourea (ENU), ethyl methanesulfonate (EMS), and diethyl nitrosamine (DEN).
  • Assessed lacZ mutant frequency in bone marrow/liver and micronucleus induction in peripheral blood.

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Main Results:

  • All tested mutagens increased lacZ mutant frequency in bone marrow or liver.
  • All mutagens except DEN induced micronuclei in peripheral blood.
  • Demonstrated tissue-specific genotoxicity detection capabilities.

Conclusions:

  • The combined assay effectively detects in vivo genotoxicity using both gene mutation and micronucleus endpoints.
  • The study highlights potential tissue-specific responses in genotoxicity testing.
  • Future advancements require overcoming cost and labor intensiveness, possibly through positive selection methods.