Bacteriophage lambda and plasmid pUR288 transgenic fish models for detecting in vivo mutations

We adapted transgenic rodent mutation assays based on fish carrying bacteri ophage lambda and plasmid pUR288 vectors to address the needs for improved methods to assess health risks from exposure to environmental mutagens and also to establish new animal models to study in vivo mutagenesis. The appro ach entails separating the vectors from fish genomic DNA and then shuttling them into specialized strains of E. coli bacteria to analyze spontaneous a nd induced mutations in either lacI and cII or lacZ mutational targets. Fis h exhibited low frequencies of spontaneous mutants comparable to the sensit ivity of transgenic rodent models. Mutations detected after treating fish w ith chemical mutagens showed concentration-dependent, tissue-specific, and time-dependent relationships. Spontaneous and induced mutational spectra al so were consistent with the specificity of known mutagens, further supporti ng the utility of transgenic fish for studies of in vivo mutagenesis.