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Boronic acids-A novel class of bacterial mutagen

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Publication Date
2011-09-18
ICR Author
Phillips, David Hunter
Author
O Donovan, MR
Mee, CD
Fenner, S
Teasdale, A
Phillips, DH
Type
Journal Article
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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 >1000 mu g/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. (C) 2011 Elsevier B.V. All rights reserved.
URL
https://repository.icr.ac.uk/handle/internal/2321
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Version of record
10.1016/j.mrgentox.2011.05.006
Research team
Human Biomonitoring & Carcinogen Activation
Language
English
License start date
2011-09-18
Citation
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2011, 724 pp. 1 - 6
Publisher
ELSEVIER SCIENCE BV

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