Mutagenicity of 2-aminopurine, 6-N-hydroxylaminopurine, and 2-amino-N6-hydroxyadenine in Neurospora crassa.

These data from our experiments with 3 purine analogs reveal striking differences in mutagenic potency. It seems highly likely that these analogs substitute readily for adenine and that they cause mutations in the main part, and in the case of AHA perhaps predominantly, by mispairing with cytosine. The most potent mutagens are those with the hydroxylamino group at the C6 position (AHA and HAP). Of these, the most potent is the analog with an amino group in the C2 position (AHA). The most interesting aspect of the present studies is their implications for other eukaryotic organisms. We have determined that AHA, which was shown to be a potent mutagen in bacteria [11], is an extremely potent mutagen in a eukaryotic organism. AHA is active at relatively low concentrations, and it gives rise to point mutations that appear to arise predominantly by AT----GC base-pair transitions. AHA should be an extremely useful genetic probe for studies on higher eukaryotic organisms. Its potency and specificity make it an unusual mutagen that can be expected to produce specific-locus mutants at high frequency with the genetic damage confined to the boundaries of the gene. These characteristics should make it useful not only for studies of specific-locus mutations and sex-linked recessive lethal mutations in Drosophila but also for specific-locus studies in mammalian cells in culture and in the whole animal. In these latter systems, it is extremely time consuming and sometimes impossible to distinguish between point mutations and multilocus deletions. The use of AHA as a mutagen in these systems should provide a useful new approach to genetic fine structure analysis.