Deletion induction in bacteria. I. The role of mutagens and cellular error-prone repair

The amber mutation trpD28 of Salmonella typhimurium shows a complex reversion pattern on anthranilate (AA)-supplemented minimal medium. Under such conditions it is possible to recover revertants of two phenotypes, prototrophs (MM+) and anthranilate utilizers (AA+), each phenotype brought about by several mutational events. Since one class of AA+ revertants is caused by deletion of the trpD28 mutation, this constitutes a useful system for quantitative studies of the effects of mutagenic agents and cellular factors on the production of deletions. In the present study we have tried to assess the relative contribution of chemical mutagens vs. cellular mutator factors in causing this class of mutations. Strains of S. typhimurium in which the spontaneous reversion rate of trpD28 was modified by pKM101, (strain SO1007), mutL (strain SO1018) and both (strain SO1008), as well as the wild type (strain SO939) were treated with nitrous acid (HNO2) and mitomycin C (MC), mutagens reported to induce deletions in bacteria. The results showed that while the absolute frequency of deletions increased exponentially with dose of mutagen in parallel with the total reversion frequency, the relative frequency (percent) of these mutations was characteristic for each strain and for the most part unaffected by the dose of mutagen. It appears that deletions, spontaneous or induced, occur as a fixed percentage of total mutations and are brought about by the cells' own repair capacity and characteristic DNA metabolism. Perhaps these mutations are the result of untargeted events during SOS misrepair.