Ames positive boronic acids are not all eukaryotic genotoxins.
Boronic acids and their derivatives have been exploited for their pharmacological activity and their utility as intermediates in the synthesis of novel non-boron containing compounds. A recent study reported that boronic acids are bacterial mutagens. Here, results are reported from the testing of nine boronic acids using the pan-mechanistic eukaryotic GADD45a genotoxicity assays, BlueScreen HC and GreenScreen HC. Positive results were produced for one compound in GreenScreen and four compounds in BlueScreen. Only negative results were produced when tested with S9 metabolic activation. These data suggest that there is not a general genotoxic liability in eukaryotes, within this chemical domain. Furthermore, they are not potent eukaryotic genotoxins: positive results were produced only at concentrations between 1mM and 10mM. Their presence as low concentration contaminants or impurities would be unlikely to produce misleading positive results for a test material.
Gentronix Ltd., BioHub at Alderley Park, Cheshire, SK10 4TG, United Kingdom.
Heather
H
Scott
Gentronix Ltd., BioHub at Alderley Park, Cheshire, SK10 4TG, United Kingdom; Faculty of Life Sciences, University of Manchester, M13 9PL, United Kingdom. Electronic address: richard.walmsley@manchester.ac.uk.
Richard M
RM
Walmsley
D001897:Boronic Acids / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D000097642:GADD45 Proteins
D001897:Boronic Acids; D018797:Cell Cycle Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases; D009153:Mutagens; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins
Ames; BlueScreen HC; Boronic acids; Eukaryotic genotoxins; GADD45a; GreenScreen HC