Induction of genetic duplications and frameshift mutations in Salmonella typhimurium by acridines and acridine mustards: dependence on covalent binding of the mutagen to DNA.
The aroC321 allele permits positive selection for the detection of a large genetic duplication that arises in the Salmonella typhimurium chromosome by homologous recombination. Strains that contain both aroC321 and the hisC3076 allele were constructed so that the induction of genetic duplications and frameshift mutations in a run of GC base pairs could be studied simultaneously by selecting for tryptophan and histidine prototrophy, respectively. Using these strains, we examined the ability of 9-aminoacridine, quinacrine, four acridine mustards (ICR-170, ICR-191, ICR-372, and quinacrine mustard) and the nitroacridine Entozon to induce genetic duplications and frameshift mutations. Although all these compounds induce reversion of hisC3076, only the four mustards and Entozon are effective as inducers of genetic duplications under identical treatment conditions. The induction of genetic duplications by acridine mustards, like the toxic and mutagenic effects of these compounds, is enhanced by a deficiency for excision repair caused by a deletion through the uvr B gene. The ineffectiveness of 9-aminoacridine and quinacrine in the test for genetic duplications indicates that simple intercalation is sufficient for the mutagenic effect measured with the hisC3076 allele but that the induction of duplications by the acridine mustards and Entozon requires covalent binding of the chemical to DNA.
Hoffmann
G R
GR
Department of Biology, College of the Holy Cross, Worcester, MA 01610.
Freemer
C S
CS
Parente
L A
LA
D000166:Acridines / Q000494:pharmacology*; D000585:Aminacrine / Q000031:analogs & derivatives; D000609:Aminoacridines; D002876:Chromosomes, Bacterial / Q000187:drug effects; D004252:DNA Mutational Analysis; D009153:Mutagens; D009154:Mutation; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D011796:Quinacrine; D011797:Quinacrine Mustard; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D014161:Transduction, Genetic
D000166:Acridines; D000609:Aminoacridines; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; C091910:acridine mustard; D011797:Quinacrine Mustard; D000585:Aminacrine; C004294:acridine half-mustard; D011796:Quinacrine