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Mammalian cell gene mutation assays working group report
C S Aaron1, G Bolcsfoldi, H R Glatt
1Upjohn Company, Kalamazoo, MI 49001.
Mutation Research
|June 1, 1994
Summary
Standardized mammalian cell gene mutation assays are crucial for genotoxicity testing. Recommendations cover concentration limits, acceptable assays, and data interpretation for reliable mutagenesis evaluation.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- International guidelines for genotoxicity testing were reviewed at a 1993 workshop.
- Focus was on protocol standardization for mammalian cell gene mutation assays.
Framework:
- Recommendations were made for upper concentration limits for toxic and non-toxic substances.
- Established assays like L5178Y TK+/- and CHO/HPRT are suitable; the ouabain system is not recommended for routine use.
- Metabolic activation (S9) is required for testing.
Implementation:
- Specific protocols for the mouse lymphoma assay (L5178Y TK+/-) were discussed, including colony sizing and positive control validation.
- Testing requires both in the presence and absence of S9 metabolic activation.
- Extended treatment times (>2 cell cycles) require strong justification.
Implications:
- Clear positive or negative results do not require repetition if the assay is well-performed, diverging from UK guidelines.
- Increased dose numbers are recommended if treatment groups are not replicated.
- Laboratories should maintain historical performance databases for assays.