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Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study

Authors :
Walter Meinl
Bernhard H. Monien
Hansruedi Glatt
Albrecht Seidel
Benjamin Sachse
Yasmin Sommer
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.

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