Alternativmethode Mikronukleustest in Fischzellen

The in vitro micronucleus (MN) test is a key method for identifying aneugenic and clastogenic substances. We are establishing and refined a testing approach based on brain-derived, strictly epithelial growing fish stem cells in a multi-center approach to
evaluate their suitability for advanced MN applications. These cells display distinct metabolic and embryonic features such as aryl hydrocarbon receptor expression. Variants expressing the histone marker H2B‑GFP enable automated kinetic live-cell imaging in a 96‑well format, providing real-time visualization of chromosomal alterations and cell cycle dynamics. In addition, types of chromosomal instability such as nuclear buds, nucleoplasmic bridges, and karyorrhectic events can be detected directly in situ.
Using model compounds, we validate the detection of aneugens and clastogens in accordance with OECD Test Guideline 487.
Preliminary data indicate that the fish cell line exhibits metabolic competence. This suggests the potential use of these cells for testing pro-genotoxins without reliance on animal-derived S9 fractions for metabolic activation. Pending further validation, fish cell models may provide a mechanistically informative, animalf-ree alternative for genotoxicity testing in accordance with the 3R principles.