ACTIVATION OF THE MAILLARD REACTION-PRODUCT 5-(HYDROXYMETHYL)FURFURALTO STRONG MUTAGENS VIA ALLYLIC SULFONATION AND CHLORINATION

5-(Hydroxymethyl)furfural (HMF), one of the major intermediate product s in the Maillard reaction, is present in a wide variety of foods. Thi s aldehyde is formed as a decomposition product of glucose and fructos e in foodstuffs subject to cooking or heat sterilization. It has been found to possess mutagenic and DNA strand-breaking activity. However, the mechanisms by which HMF exerts its genotoxicity remain unclear. Th e present study was undertaken to determine if HMF could be metabolica lly activated via esterification of the allylic hydroxyl group. In sup port of this concept, the chemically synthesized sulfuric acid eater, 5-[(sulfooxy)methyl]furfural (SMF), exhibited direct mutagenicity at b oth thymidine kinase and hypoxanthine-guanine phosphoribosyltransferas e loci in human lymphoblasts. This reactive ester also induced 8-azagu anine-resistant mutants in Salmonella typhimurium TM677 in a dose-depe ndent manner. The intrinsic mutagenicity pf SMF was enhanced by additi on of extra chloride ion to the assay medium. The model allylic deriva tive, 5-(chloromethyl)furfural, was also mutagenic and cytotoxic in ba cteria, but much more active than the sulfuric acid ester in this rega rd. In contrast to (sulfooxy)methyl and chloromethyl derivatives of HM F, 2-[(sulfooxy)-methyl]- and 2-(chloromethyl)furans which lack the al dehyde functionality did not exhibit significant mutagenicity. Rodent hepatic cytosols contained sulfotransferase activity responsible for t he formation of the reactive allylic sulfuric acid eater metabolite fr om HMF.