Other investigators have shown that several polycyclic carcinogens are frameshift mutagens in Salmonella. Mutagenic potency of these compounds is assessed by ability to induce reversion of histidine-requiring frameshift mutants to prototrophy. One frameshift mutation in the histidinol dehydrogenase gene, hisD3052, is unusually sensitive to mutagenesis by certain polycyclic carcinogens. We find that the 3052 mutation is a -1 deletion, probably loss of a G C pair from a DNA repeat of -G-G-G--C-C-C-. The polycyclic carcinogens tested (e.g., 2-nitroso- Frameshift mutations result from additions (+) or deletions (-) of DNA base pairs from genes encoding polypeptide chains, so that triplets in the product mRNA are not read in the correct frame after the mutation (7,8). Correction of such mutations may occur by restoration of the original base sequence, or by introduction of a closely positioned frameshift of opposite sign. In these double frameshift mutants (+ -) the normal reading frame is restored in mRNA except for the segment between the two frameshifts. The (+ -) mRNA segment encodes a segment of altered amino acids in the polypeptide chain, often disturbing its function. Sequencing the affected polypeptide segment allows reconstruction of associated mRNA and DNA sequences (9, 10). The hisD gene encodes the enzyme histidinol dehydrogenase (EC 1.1.1.23). To determine nucleic acid base changes in 3052 caused by polycyclic carcinogens and other frameshift mutagens, we have induced reversion in 3052 by these compounds. Revertants carrying double frameshift mutations were detected by rapid screening of crude extracts from revertants for altered histidinol dehydrogenase. The altered enzyme from each double mutant was then purified and compared with the normal enzyme by peptide mapping to detect altered peptides. These were sequenced to reconstruct altered DNA sequences in 3052 and its revertants. We have also classified the reversions with respect to certain properties of histidinol dehydrogenase from crude extracts, and have correlated the classes of reversion with specific DNA sequence changes.We believe that this newly characterized tester system will be useful for rapid screening of carcinogens as frameshift mutagens. For the relatively small effort of inducing reversions in 3052 with carcinogens or other mutagens and examining crude extract histidinol dehydrogenase, it should be possible to assign the reversions to the standard groups with known base sequence changes in DNA (see below).

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