Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-(Hydroxymethyl)furfural (HMF), one of the major intermediate products in the Maillard reaction, is present in a wide variety of foods. This aldehyde is formed as a decomposition product of glucose and fructose 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. The present study was undertaken to determine if HMF could be metabolically activated via esterification of the allylic hydroxyl group. In support of this concept, the chemically synthesized sulfuric acid ester,5-[(sulfooxy)-methyl]furfural (SMF), exhibited direct mutagenicity at both thymidine kinase and hypoxanthine-guanine phosphoribosyltransferase loci in human lymphoblasts. This reactive ester also induced 8-azaguanine-resistant mutants in Salmonella typhimurium TM677 in a dose-dependent manner. The intrinsic mutagenicity of SMF was enhanced by addition of extra chloride ion to the assay medium. The model allylic derivative, 5-(chloromethyl)furfural, was also mutagenic and cytotoxic in bacteria, but much more active than the sulfuric acid ester in this regard. In contrast to (sulfooxy)methyl and chloromethyl derivatives of HMF,2-[(sulfooxy)-methyl]- and 2-(chloromethyl)furans which lack the aldehyde functionality did not exhibit significant mutagenicity. Rodent hepatic cytosols contained sulfotransferase activity responsible for the formation of the reactive allylic sulfuric acid ester metabolite from HMF.
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PMID:Activation of the Maillard reaction product 5-(hydroxymethyl)furfural to strong mutagens via allylic sulfonation and chlorination. 807 62

5-(hydroxymethyl)-2-furfural (HMF), a common product of the Maillard reaction, occurs in many foods in high concentrations, sometimes exceeding 1 g/kg (in certain dried fruits and caramel products). The toxicological relevance of this exposure has not yet been clarified. Induction of aberrant colonic crypt foci had been reported for HMF, in vitro studies on genotoxicity/mutagenicity have given controversial results. To elucidate the toxic potential of HMF, cytotoxicity (trypan blue exclusion), growth inhibition (SRB assay), mutagenicity (HPRT assay), DNA damage (single-cell gel electrophoresis) and depletion of cellular glutathione were investigated in mammalian cells. Genotoxicity (SOS repair) was monitored in Salmonella typhimurium (umu assay). HMF induced moderate cytotoxicity in V79 cells (LC(50): 115 mM, 1 hr incubation) and in Caco-2 cells (LC(50): 118 mM, 1 hr incubation). Growth inhibition was monitored following 24 hr of incubation (V79, IC(50): 6.4 mM). DNA damage was detectable neither in these cell lines nor in primary rat hepatocytes up to the cytotoxic threshold concentration (75% absolute viability). Likewise, in primary human colon cells, obtained from biopsy material, DNA damage was not measurable. At 120 mM, already exhibiting some reduction in cell viability, HMF was weakly mutagenic at the hprt-locus in V79 cells (mutants/10(6) cells: HMF 120 mM: 16 vs control: 3). Intracelluar glutathione was depleted by HMF (>/=50 mM) in V79 cells, in the human colon adenocarcinoma cell line Caco-2 and in primary rat hepatocytes down to approximately 30% of control (120 mM). Genotoxicity was observed with HMF in the umu assay without external activation (16 mM: 185 rel. umu units, %, P<0.001). The genotoxic potential was not altered by addition of rat liver microsomes. By comparison, the natural flavour constituent (E)-2-hexenal (HEX) was already cytotoxic, mutagenic and depleted glutathione at about 1000-fold lower concentrations. It induced DNA damage in mammalian cells (200-400 microM). These results suggest that HMF does not pose a serious health risk, even though the highest concentrations in specific foods approach the biologically effective concentration range in cell systems.
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PMID:5-Hydroxymethylfurfural: assessment of mutagenicity, DNA-damaging potential and reactivity towards cellular glutathione. 1093 Jul 1