Effect of Acetyl Salicyilic Acid on Glycation and Mutability of Escherichia Coli Chromosomal DNA

ABSTRACT

Recently, we have shown that the process of non-enzymatic glycosylation (glycation) affects Escherichia coli chromosomal DNA under physiological conditions in vivo. We have further demonstrated that chromosomal DNA glycation is a source of spontaneous mutations in E. coli. The present study reveals that inhibition of glycation does not necessarily lead to suppression of DNA mutability. We tested the effect of acetyl salicylic acid (ASA) on chromosomal DNA glycation and spontaneous mutagenesis in E. coli. At a concentration of 0.1 mM in the growth medium ASA proved to be non-toxic and inhibits significantly glycation of E. coli chromosomal DNA. At a concentration of 5 mM ASA partially suppressed bacterial growth but had negligible impact on DNA glycation. Most importantly, at both concentrations tested ASA caused an increase in the frequency of spontaneous reversions from Arg⁻ to Arg⁺ phenotype. In addition, we observed an accelerated hydrolysis of DNA in ASA solutions as compared to that in solutions of hydrochloric acid at the same pH. The latter result suggests a possible interaction of ASA with DNA, which explains the observed genotoxicity of ASA.

Keywords:

• acetyl salicylic acid
• ASA
• glycation
• non-enzymatic glycosylation
• inhibition of glycation
• spontaneous mutagenesis
• E. coli