Use of a new DNA intercalating fluorescing probe for studies on the mechanism of frameshift mutagenesis in Salmonella typhimurium.
As a general rule, ellipticine derivatives are mutagenic and intercalate into double-stranded nucleic acids. We have tested a new fluorescent ellipticine compound, 10[(1-carboxy-2-methylpropylidene)-amino]-9-hydroxy-2-methylell ipticinium (val-NMHE), for establishing the relationship between the amount of drug bound to nucleic acids in situ in Salmonella typhimurium and its biological effects: decrease of growth rate and mutagenesis. Val-NMHE is mutagenic only on Ames'strain TA 1977 which carries a + 1 frameshift mutation. On a per cell basis, the number of revertants is not linearly correlated to the amount of drug bound to nucleic acids: this number is relatively higher for increasing amounts of drug. This effect is not related to the mere probability of interaction between the drug molecule and its target, a GGGG/CCCC sequence. It might be explained by other hypotheses briefly discussed herein.
D000470:Alkaloids / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism*; D004611:Ellipticines / Q000378:metabolism* / Q000494:pharmacology; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D009152:Mutagenicity Tests; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013050:Spectrometry, Fluorescence
D000470:Alkaloids; D004269:DNA, Bacterial; D004611:Ellipticines; D005456:Fluorescent Dyes; D007364:Intercalating Agents; C046718:10-((1-carboxy-2-methylpropylidene)amino)-9-hydroxy-2-methylellipticinium