Evaluation of transgenic fish for detecting in vivo mutations

Transgenic medaka and mummichog were developed that carry multiple copies of either lambda bacteriophage, or plasmid vectors that harbor target genes (lacZ, lacI, or cII) for mutation detection. The common approach used in the three mutation assays entails exposing fish to a potential mutagen, followed by recovering the vector from the genomic DNA, and quantifying mutations in the target genes via indicator bacteria. A number of features of the fish mutation assays were evaluated related to their potential utility in genotoxicology. The vectors were recovered from transgenic fish genomic DNA with efficiencies that surpassed those of transgenic mice that carry identical vectors. The spontaneous mutation frequencies of the three target genes obtained from the fish were comparable to one another, as well as, to transgenic mice. The induction of mutations following chemical mutagen exposure indicated predictable and sensitive responses. Individual mutations were examined to provide spontaneous and induced mutational spectra. These analyses demonstrate that the fundamental requirements for mutation detection using transgenic fish have been met.