Mutagenicity testing with transgenic mice. Part I: Comparison with the mouse bone marrow micronucleus test

Area of Science:

• Toxicology
• Genetics
• Biotechnology

Background:

• Transgenic animal models are increasingly used in mutagenicity testing.
• Traditional methods like the mouse bone marrow micronucleus test are well-established.
• Comparing these methods is crucial for understanding their respective strengths.

Purpose of the Study:

• To compare the results of transgenic mouse mutagenicity assays (lacI and lacZ models) with the mouse bone marrow micronucleus test.
• To evaluate the concordance between gene mutation detection in transgenic models and chromosome aberration detection in the micronucleus test.
• To identify the advantages and complementary roles of each testing system.

Main Methods:

• Literature review of 39 substances tested in both transgenic mouse assays (Big Blue mouse, Mutatrade markMouse) and the mouse bone marrow micronucleus test.
• Comparative analysis of test outcomes for the same substances across different mutagenicity testing platforms.

Main Results:

• A majority of the 39 substances showed agreement between the transgenic mouse assays and the micronucleus test.
• Despite examining different genetic endpoints (gene mutation vs. chromosome aberration), the results were largely consistent.
• Transgenic assays detected systemic and local mutagenic effects, unlike the organ-specific micronucleus test.

Conclusions:

• Transgenic mouse assays and the micronucleus test are complementary in mutagenicity testing.
• Transgenic assays provide a broader scope by not being restricted to a single target organ.
• Both methods have distinct advantages and contribute valuable, albeit different, information in genotoxicity assessment.