OVERVIEW OF MUTATION ASSAYS IN TRANSGENIC MICE FOR ROUTINE TESTING

There is scientific and regulatory interest in using mutation assays i n transgenic mice in safety assessments for new chemicals and drugs. C urrently these assays ore in the process of being validated, and proto cols for routine testing are being defined. Some of the issues and res ults to date with regard to assay validation include reproducibility o f the assay results (they are qualitatively reproducible), relevance o f the test system (the transgene closely approximates on endogenous ma mmalian gene as a mutational target for the limited number of compound s tested), and the predictivity of the assay for heritable effects (un known at this time) or carcinogenicity (the assays show good positive predictivity for carcinogenicity; the negative predictivity of the ass ay requires further investigation). Definition of appropriate study pr otocols for routine testing requires that applicable statistical metho ds are available and that the experimental parameters that affect the detection of mutations are known. Progress mode in identifying these p arameters is discussed. A proposal is mode for the custom design of ro utine safety studies, which is based on the anticipated use of each in dividual test agent. A working group has been formed to conduct some o f the studies still required for validation of these essays. (C) 1995 Wiley-Liss, Inc.