Mammalian germ cell mutagenicity of ENU, IPMS and MMS, chemicals selected for a transgenic mouse collaborative study

Area of Science:

• Genetics and Molecular Biology
• Toxicology
• Mammalian Genetics

Background:

• Transgenic mouse mutation assays are increasingly used for genetic toxicology.
• Assessing germ cell mutagens is crucial for understanding heritable genetic damage.
• Traditional mutagenicity assays provide a basis for comparison with newer transgenic methods.

Purpose of the Study:

• To systematically assess the utility of transgenic mouse mutation assays as screens for germ cell mutagens.
• To compare the performance of transgenic assays with established non-transgenic assays for known germ cell mutagens.
• To summarize the DNA reactivity and mutation characteristics of selected germ cell mutagens.

Main Methods:

• Review of existing literature on three male mouse germ cell mutagens: ENU, N-ethyl-N-nitrosourea (ENU), N-isopropyl-N-methyl-N-nitrosoguanidine (iPMS), and methyl methanesulfonate (MMS).
• Comparison of data from transgenic assays with results from non-transgenic assays: dominant lethal test, heritable translocation test, and specific locus test.
• Summary of information regarding the DNA reactivity and molecular nature of mutations induced by ENU, iPMS, and MMS.

Main Results:

• ENU, iPMS, and MMS are known male mouse germ cell mutagens.
• Existing data from non-transgenic assays (dominant lethal, heritable translocation, specific locus tests) are available for these chemicals.
• Information on DNA reactivity and the molecular basis of mutations induced by these mutagens has been compiled.

Conclusions:

• Transgenic mouse mutation assays show promise as screens for germ cell mutagens.
• Comparative analysis with established assays is essential for validating new methods.
• Understanding chemical-induced DNA reactivity and mutation spectra informs risk assessment.