Back to Search
Start Over
Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study
- Source :
- Archives of Toxicology, Archives of toxicology, 90(1): 137–148
- Publisher :
- Springer Nature
-
Abstract
- 5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent rodent carcinogens that are present in thermally processed foodstuffs. The carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)-mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous SULT forms substantially differ in substrate specificity and tissue distribution. This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and rats. The catalytic efficiencies (kcat/KM) of HMF sulfoconjugation of human SULT1A1 (13.7 s−1 M−1), mouse Sult1a1 (15.8 s−1 M−1) and 1d1 (4.8 s−1 M−1) and rat Sult1a1 (5.3 s−1 M−1) were considerably higher than those of all other SULT forms investigated (≤0.73 s−1 M−1). FFA sulfoconjugation was monitored using adenosine as a nucleophilic scavenger for the reactive 2-sulfoxymethylfuran (t1/2 = 20 s at 37 °C). The resulting adduct N6-((furan-2-yl)methyl)-adenosine (N6-MF-A) was quantified by isotope-dilution UPLC-MS/MS. The rates of N6-MF-A formation showed that hSULT1A1 and its orthologues in mice and rats were also the most important contributors to FFA sulfoconjugation in each of the species. Taken together, the catalytic capacity of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which carcinogenic effects of HMF and FFA were detected. This is of primary concern due to the expression of hSULT1A1 in many different tissues. Electronic supplementary material The online version of this article (doi:10.1007/s00204-014-1392-6) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Sulfotransferase
Health, Toxicology and Mutagenesis
Food Contamination
Toxicology
Risk Assessment
Catalysis
Scavenger
Adduct
Furfuryl alcohol
Activation, Metabolic
03 medical and health sciences
chemistry.chemical_compound
Species Specificity
Nucleophile
Tandem Mass Spectrometry
medicine
Humans
Furaldehyde
Furans
Carcinogen
5-Hydroxymethylfurfural
Food carcinogens
General Medicine
Arylsulfotransferase
Adenosine
Recombinant Proteins
Isoenzymes
Kinetics
Metabolic pathway
030104 developmental biology
chemistry
Biochemistry
UPLC-MS/MS
Carcinogens
Chromatography, Liquid
Toxicokinetics and Metabolism
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 03405761
- Volume :
- 90
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Archives of Toxicology
- Accession number :
- edsair.doi.dedup.....99d4b118301b60c49df0df34939238c4
- Full Text :
- https://doi.org/10.1007/s00204-014-1392-6