Bioactivation of 5-Hydroxymethyl-2-Furaldehyde to an Electrophilic and Mutagenic Allylic Sulfuric Acid Ester

Lee, Young Choon; Shlyankevich, Mark; Jeong, Hee-Kyung; Douglas, James S.; Surh, Young‐Joon

doi:10.1006/bbrc.1995.1596

Cited by 91 publications

(63 citation statements)

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“…SMF may cross-link target cell DNA thereby exerting its toxic effects. The 5-sulfooxymethyl group can covalently bind to DNA bases by the S N 1 or S N 2 mechanism, and the C 2 aldehyde functional group may interact with other nucleophilic sites on DNA [Lee et al, 1995]. Moreover, the mutagenicity of SMF could be enhanced by the addition of extra chloride ions to the assay medium.…”

Section: Carcinogenic Toxic and Mutagenic Activities Of Hmfmentioning

confidence: 99%

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5-Hydroxymethyl-2-Furfural (HMF) – Heat-Induced Formation, Occurrence in Food and Biotransformation - a Review

Kowalski¹,

Łukasiewicz²,

Duda-Chodak³

et al. 2013

Pol. J. Food Nutr. Sci.

125

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The chemical structure of 5-hydroxymethyl-2-furfural (HMF), its physicochemical properties and reactions that lead to the synthesis of HMF were discussed. Special attention was paid to HMF formation in food during processing. The potential applications of this compound in industry were described as well. Moreover, this review outlines the most important sources of HMF in human diet and estimates the potential daily intake of HMF by consumers. The known and suggested metabolic pathways, as well as the impact of HMF and its metabolites on human health are also discussed.

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Section: Carcinogenic Toxic and Mutagenic Activities Of Hmfmentioning

confidence: 99%

“…HMF has especially been used for this purpose for a long time. On the other hand, HMF present in foodstuffs, seems to be studied extensively not only as a useful index of thermal processing but also as a food contaminant with potential harmful properties [Lee et al, 1995;Hiramoto et al, 1996 …”

Section: Introductionmentioning

confidence: 99%

5-Hydroxymethyl-2-Furfural (HMF) – Heat-Induced Formation, Occurrence in Food and Biotransformation - a Review

Kowalski¹,

Łukasiewicz²,

Duda-Chodak³

et al. 2013

Pol. J. Food Nutr. Sci.

125

View full text Add to dashboard Cite

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“…Indeed, the mutagenic effect could be partly suppressed by the addition of sulphotransferase inhibitors. In accordance, SMF in TA104 was genotoxic in the absence of any metabolic system (cytotoxicity not specified); the effect was reduced by addition of glutathione (GSH) and GSH-transferases and restored when this latter enzyme was inhibited (Lee et al, 1995b).…”

Section: Subgroup Iamentioning

confidence: 87%

Scientific Opinion on Flavouring Group Evaluation 67, Revision 1 (FGE.67Rev.1): Consideration of 40 furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers evaluated by J

Flavourings¹

2011

EFSA Journal

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 33 furan‐substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers evaluated by the JECFA. In the present version of FGE.67 eight additional substances have been included. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure‐activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. For twenty‐two substances [FL‐no: 13.029, 13.030, 13.045, 13.052, 13.054, 13.059, 13.061, 13.066, 13.069, 13.070, 13.083, 13.092, 13.101, 13.103, 13.105, 13.106, 13.107, 13.123, 13.138, 13.148, 13.163 and 13.191] a concern for genotoxicity was raised and therefore these were not evaluated using the Procedure. The Panel concluded that 8 substances [FL‐no: 13.006, 13.021, 13.022, 13.023, 13.024, 13.074, 13.116 and 13.190] do not give rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach. For one substance [FL‐no: 13.058] additional toxicity data are requested. Besides the safety assessment of these substances, the specifications for the materials of commerce have been considered. For three substances [FL‐no: 13.031, 13.045 and 13.047] data on specifications / stereoisomerism are missing.

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“…HMF by gavage for 5 days per week for 104 weeks, the incidence of hepatocellular adenomas was significantly increased in treated female mice (NTP, 2010). Numerous studies have been performed to investigate HMF genotoxicities, with Ames tests, comet assay and in vivo micronucleus tests showing negative results, as did sister chromatid exchange test, HPRT and umu assays, except at respective toxic doses Lee et al, 1995;Janzowski et al, 2000;Glatt et al, 2005;NTP 2010). However, 5-sulfoxymethylfurfural (SMF), a HMF metabolite produced following sulfotransferase (SULT) conjugation, did have strong mutagenicity in vitro Lee et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have been performed to investigate HMF genotoxicities, with Ames tests, comet assay and in vivo micronucleus tests showing negative results, as did sister chromatid exchange test, HPRT and umu assays, except at respective toxic doses Lee et al, 1995;Janzowski et al, 2000;Glatt et al, 2005;NTP 2010). However, 5-sulfoxymethylfurfural (SMF), a HMF metabolite produced following sulfotransferase (SULT) conjugation, did have strong mutagenicity in vitro Lee et al, 1995). Indeed, HMF yielded positive results in an Ames test in the presence of rat liver cytosol containing 3'-phosphoadenosine-5'-phosphosulfate (Lee et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Reporter gene mutation in the livers of <i>gpt</i> delta mice treated with 5-(hydroxymethyl)-2-furfural, a contaminant of various foods

et al. 2012

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-A major product formed during the Maillard reaction is 5-(hydroxymethyl)-2-furfural (HMF), which is present in various foods and beverages such as honey and fruit juice. HMF was shown to be a hepatocarcinogen in female mice using long-term bioassays. Although HMF is not a mutagen in conventional in vitro mutation assays, 5-sulfoxymethylfurfural (SMF), a reactive metabolite of HMF produced following sulfotransferase conjugation, does show mutagenicity. Thus, HMF-induced hepatocarcinogenesis likely involves genotoxic mechanisms. To clarify the mechanisms underlying HMF-induced hepatocarcinogenesis, female B6C3F 1 gpt delta mice were given HMF at carcinogenic doses (188 or 375 mg/kg b.w.) by gavage for 5 days per week for 4 weeks. This treatment produced no significant differences in mutant frequencies (MFs) of gpt and red/gam (Spi -) genes among the groups. These results suggest that genotoxicity does not contribute to HMF-induced hepatocarcinogenesis. Parameters related to cell proliferation, such as proliferation cell nuclear antigen-labeling index and Cyclin D1 and E1 mRNA expression, exhibited no significant changes in the livers of HMF-treated groups. In view of the lack of carcinogenicity in rats, HMF may be considered to be a weak carcinogen. These results help us to understand the underlying mechanisms of action of HMF carcinogenesis.Key words: 5-(hydroxymethyl)-2-furfural, 5-sulfoxymethylfurfural, gpt delta mice, in vivo mutagenicity Correspondence: Takashi Umemura (E-mail: umemura@nihs.go.jp) LetterThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.37, No.5, 1077-1082, 2012 1077 T1A1 (Glatt et al., 2005T1A1 (Glatt et al., , 2012. The presence of SMF in the serum of mice to which HMF was administered intravenously (Monien et al., 2009), strongly supports the involvement of SMF in HMF-induced hepatocarcinogenesis.Reporter gene mutation assays are useful tools for investigating in vivo mutagenicity of environmental agents (WHO, 2006). The remarkable advantage of these assays is that the absorption, distribution, metabolism and excretion of test chemicals can be taken into account (Nohmi et al., 2000). In the present study, we performed an in vivo mutation assay with HMF using B6C3F 1 gpt delta female mice and the same conditions as the long-term bioassay, along with measurements of the proliferation cell nuclear antigen (PCNA) labeling index of hepatocytes and mRNA expression levels of several cell cycle-related genes. MATERIALS AND METHODS Experimental animals and housing conditionsThe protocol for this study was approved by the Animal Care and Utilization Committee of the National Institute of Health Sciences. Female B6C3F 1 gpt delta mice carrying 80 tandem copies of the transgene lambda EG10 in haploid genome were raised by mating C57BL/6 gpt delta and non-transgenic C3H/He mice (Japan SLC, Inc., Shizuoka, Japan). 15 female B6C3F 1 gpt delta mice were each randomized by weight into three groups. The mice were housed in a room with a barrier system and maintained under constant tempe...

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Bioactivation of 5-Hydroxymethyl-2-Furaldehyde to an Electrophilic and Mutagenic Allylic Sulfuric Acid Ester

Cited by 91 publications

References 0 publications

5-Hydroxymethyl-2-Furfural (HMF) – Heat-Induced Formation, Occurrence in Food and Biotransformation - a Review

5-Hydroxymethyl-2-Furfural (HMF) – Heat-Induced Formation, Occurrence in Food and Biotransformation - a Review

Scientific Opinion on Flavouring Group Evaluation 67, Revision 1 (FGE.67Rev.1): Consideration of 40 furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers evaluated by J

Reporter gene mutation in the livers of <i>gpt</i> delta mice treated with 5-(hydroxymethyl)-2-furfural, a contaminant of various foods

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