5-Sulfooxymethylfurfural as a possible ultimate mutagenic and carcinogenic metabolite of the Maillard reaction product, 5-hydroxymethylfurfural.
Heat treatment of foods containing reducing sugars and amino acids during cooking or sterilization triggers a sequence of non-enzymatic reactions collectively known as the Maillard reaction. 5-Hydroxymethylfurfural (HMF), one of the major intermediate products in the Maillard reaction, has been found to possess cytotoxic, genotoxic and tumorigenic activities, but the mechanisms of its toxic actions remain unclear. Formation of an electrophilic allylic ester bearing a good leaving group such as sulfate has been proposed as a possible metabolic activation pathway for HMF. In order to further test this possibility, we compared the mutagenic and carcinogenic activities of HMF and its chemically synthesized sulfuric acid ester, 5-sulfooxymethylfurfural (SMF). SMF induced dose-dependent increases in the number of His+ revertants in Salmonella typhimurium TA100. This intrinsic mutagenicity of SMF was significantly inhibited by ascorbic acid added to the assay media. In the presence of chloride ions, the bacterial mutagenicity of the highly polar sulfuric acid ester of HMF may also be mediated by formation of a lipophilic chloromethyl derivative. When topically applied to mouse skin, both sulfooxymethyl and chloromethyl derivatives of HMF exhibited higher skin tumor initiating activity than the parent hydroxymethyl compound. 5-Chloromethylfurfural was found to be a strong hepatocarcinogen in infant male B6C3F1 mice.
Surh
Y J
YJ
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034.
Liem
A
A
Miller
J A
JA
Tannenbaum
S R
SR
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D005260:Female; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
C090107:5-sulfooxymethylfurfural; D002273:Carcinogens; D009153:Mutagens; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde