COMPARISON OF THE TYPES OF MUTATIONS INDUCED BY 7,12-DIMETHYLBENZ[A]ANTHRACENE IN THE LACL AND HPRT GENES OF BIG BLUE(R) RATS

An important question regarding the use of transgenic reporter genes t o detect mutation in rodents is how the types of mutations recovered i n transgenes compare with the types of mutations found in endogenous g enes. In this study, we examined mutations induced by 7,12-dimethylben z[a]anthracene in the loci transgene and the endogenous hprt gene of l ymphocytes From Big Blue(R) rats and in the hprt gene of lymphocytes f rom nontransgenic Fischer 344 rats. The overall mutation profiles foun d in these genes were remarkably similar: the majority of mutations we re base pair substitutions, with the most common mutation being A:T -- > T:A transversion. Differences were found for the mutational profiles in the endogenous gene and transgene with respect to the location of the mutations and the orientation of basepair substitutions in the DNA strands. In most cases, these differences could be explained by the n ature of the target genes. The results support the use of the loci tra nsgene for detecting in vivo mutation. (C) 1998 Wiley-Liss, Inc.