MODIFICATION OF THE AMINO GROUP OF GUANOSINE BY METHYLGLYOXAL AND OTHER ALPHA-KETOALDEHYDES IN THE PRESENCE OF HYDROGEN-PEROXIDE

Methylglyoxal is directly mutagenic to Salmonella typhimurium TA100 an d its mutagenicity is markedly enhanced in the presence of hydrogen pe roxide. We found that methylglyoxal in phosphate buffer was decomposed easily by hydrogen peroxide at room temperature:to yield acetic acid and formic acid as major products and diacetyl as a minor product; ace tyl radical was detected in the solution by ESR spectroscopy by the us e of a spin-trapping reagent, 5,5-dimethyl-1-pyrroline N-oxide. Furthe rmore, guanosine was converted into N2-acetylguanosine by a combinatio n of methylglyoxal and hydrogen peroxide in 0.1 M phosphate buffers (p H 6.1 to 7.4). This acetylation may be related to the enhancement of m ethylglyoxal mutagenicity by hydrogen peroxide. Other alpha-ketoaldehy des such as glyoxal and phenylglyoxal also yielded the corresponding a cids and alpha-dicarbonyls upon reaction with hydrogen peroxide under the same conditions as above. These acids would have been produced thr ough Baeyer-Villiger reaction or coupling of acyl radical with hydroxy radical, and dicarbonyls by dimerization of acyl radicals. In additio n, when phenylglyoxal was used, the generation of benzoyl radical and the conversion of guanosine to N2-benzoylguanosine were observed. Howe ver, it remains to be established whether the generation of acyl radic als is directly involved in the N-2 acylation of guanosine.