Comparative potencies of induction of point mutations and genetic duplications by the methylating agents methylazoxymethanol and dimethyl sulfate in bacteria.
Methylazoxymethanol (MAM) and dimethyl sulfate (DMS) are mutagens whose genetic effects can be ascribed to the methylation of DNA. While both methylate the N7 position of guanine heavily, only MAM strongly methylates the O(6) position of guanine. We evaluated the relative effectiveness and specificity of MAM and DMS in bacterial assays for the induction of point mutations and the formation of chromosomal duplications by genetic recombination. Salmonella typhimurium strain TS1121 was used to measure the formation of genetic duplications on the basis of the aroC321 allele and mutations by reversion of the hisG46 allele. Specific base pair substitutions and frameshift mutations were measured in a reversion assay based on lacZ alleles of Escherichia coli. The results show MAM to be the more potent mutagen and DMS the stronger recombinagen in the Salmonella assay. In the lacZ assay DMS induced several classes of base pair substitutions (GC-->AT transitions, GC-->TA transversions and AT-->TA transversions), as well as lower frequencies of +1, -1 and -2 frameshift mutations. The activity of MAM as a base pair substitution mutagen was more specific than that of DMS, inducing only GC-->AT transitions. It also induced +G, -G, -A and -CG frameshift mutations, though more weakly than it induced GC-->AT transitions. Long known as a base pair substitution mutagen, the induction of frameshifts by MAM was unexpected. The results show that both DMS and MAM are effective inducers of base pair substitutions and modest inducers of frameshifts and that DMS exhibits a broader spectrum of mutagenic activity than does MAM.
Department of Biology, College of the Holy Cross, Worcester, MA 01610, USA. ghoffmann@holycross.edu
George R
GR
Hoffmann
David J
DJ
Crowley
Pia J
PJ
Theophiles
D000483:Alleles; D020029:Base Pairing / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D004260:DNA Repair; D004269:DNA, Bacterial; D020440:Gene Duplication / Q000187:drug effects*; D006639:Histidine / Q000378:metabolism; D007763:Lac Operon / Q000502:physiology; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation / Q000187:drug effects*; D011995:Recombination, Genetic / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism
D002273:Carcinogens; D004269:DNA, Bacterial; D009153:Mutagens; D013463:Sulfuric Acid Esters; D006639:Histidine; D008746:Methylazoxymethanol Acetate; D014364:Tryptophan; C019895:chorismate synthase; D019761:Phosphorus-Oxygen Lyases; C030667:methylazoxymethanol; C007482:dimethyl sulfate