title: Boronic acids-a novel class of bacterial mutagen.
abstract: Boronic acids and their esters are important building blocks in organic syntheses including those for drug substances and for which, as far as it can be determined, there are no published reports of testing for genotoxicity. A number of boronic acids have now been tested in this laboratory using Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA(pKM101). Twelve of the 13 structures presented here were found to be mutagenic. All the compounds except one were active only in TA100 and/or WP2uvrA(pKM101), did not require S9 activation and produced relatively weak responses, i.e. no more than seven times the concurrent solvent-control values at >1000μg/plate. The single exception was also weakly mutagenic for TA1537 in the presence of S9. Results with two compounds mutagenic for both TA100 and WP2uvrA(pKM101) showed no evidence of DNA-adduct formation detectable by (32)P-postlabelling. It appears that boronic acids represent a novel class of bacterial mutagen that may not act by direct covalent binding to DNA. However, their mechanism of action remains to be elucidated and it cannot yet be determined whether or not they present a real genotoxic hazard.
authors.affiliation: Astrazeneca R&D, Alderley Park, Macclesfield, SK10 4TG, UK. mike.odonovan@astrazeneca.com
authors.forename: Michael R
authors.initials: MR
authors.lastname: O'Donovan
authors.forename: Christine D
authors.initials: CD
authors.lastname: Mee
authors.forename: Simon
authors.initials: S
authors.lastname: Fenner
authors.forename: Andrew
authors.initials: A
authors.lastname: Teasdale
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001711:Biotransformation; D001897:Boronic Acids / Q000633:toxicity*; D006224:Cricetinae; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D001897:Boronic Acids; D009153:Mutagens