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Evaluation of the DNA damaging effect of the heat-induced food toxicant 5-hydroxymethylfurfural (HMF) in various cell lines with different activities of sulfotransferases
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2009 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 47, no 4, 880-884 p.Article in journal (Refereed) Published
Abstract [en]

5-Hydroxymethylfurfural (HMF), a heat-induced food toxicant present in a vast number of food items, has been suggested to be genotoxic after being bioactivated by the sulfotransferase SULT1A1. The comet assay was used to evaluate the DNA damaging effect of HMF in cell lines with different activities of SULT1A1: two human cell lines (Caco-2, low   activity; and HEK293, higher activity), one cell line from mouse (L5178Y, no activity) and two cell lines from Chinese hamster (V79, negligible activity; and V79-hP-PST, high activity of human SULT1A1). HMF induced significant DNA damage in all cell lines after 3 h exposure to 100 mM. Most sensitive were V79 and V79-hP-PST where HMF induced significant DNA damage at 25 mM. Consequently, in the present study we have shown that HMF is a DNA damaging agent in vitro independent of the activity of SULT1A1 in the cells. The HMF-induced DNA damage was only observed at rather high concentrations which usually was associated with a concomitant decrease in cell viability.

Place, publisher, year, edition, pages
2009. Vol. 47, no 4, 880-884 p.
Keyword [en]
5-Hydroxymethylfurfural, Sulfotransferase, Comet assay in vitro
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-97344DOI: 10.1016/j.fct.2009.01.022ISI: 000264623000031PubMedID: 19271322OAI: oai:DiVA.org:uu-97344DiVA: diva2:172237
Available from: 2008-05-19 Created: 2008-05-19 Last updated: 2010-08-03Bibliographically approved
In thesis
1. The effect on chromosomal stability of some dietary constituents
Open this publication in new window or tab >>The effect on chromosomal stability of some dietary constituents
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

When food is heated, a vast number of compounds are formed. Some of these are known to be toxic. Among these are furan, HMF, PhIP, IQ, and MeIQx, the subjects of this thesis. All these compounds are known or suspected carcinogens but the detailed mechanisms behind their carcinogenicity have not yet been fully examined.

The aim of this thesis was to study genotoxic properties of these compounds using both in vitro and in vivo methods. Clastogenic effects of all five compounds were assessed with the flow cytometer-based micronucleus assay in vivo and for furan also with the micronucleus assay in vitro. DNA-damaging effects of HMF were studied using the comet assay. No induction of micronuclei was obtained after exposure to IQ, MeIQx or furan. Hence, it can be argued that non-genotoxic mechanisms are partly responsible for the carcinogenic properties of these compounds. PhIP, on the other hand, generated a clear response in the in vivo test. Comparing these result with previous results on acrylamide indicates that PhIP is much more potent. However, acrylamide probably poses a higher risk for humans as the intake is considerably higher.

For HMF no effects were seen using the in vivo setup. To further investigate the influence of bioactivation of HMF by sulfotransferases (SULTs) the comet assay was performed in cell lines expressing different levels of SULT. However, no correlation between SULT-expression and DNA-damage was observed. Thus, the DNA-damaging effects found in our experimental setup is probably due to other factors than SULT mediated effects.

Furthermore, in this thesis the effects of folic acid on chromosomal stability in healthy people were studied. A negative correlation was found between micronucleus frequency and folate status. The results gained within this thesis will hopefully contribute to the risk assessment of compounds present in our diet.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 50 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 446
Biology, Genotoxicity, chromosomal stability, heterocyclic amines, furan, HMF, folic acid, micronucleus test, comet assay, Biologi
urn:nbn:se:uu:diva-8922 (URN)978-91-554-7233-7 (ISBN)
Public defence
2008-06-13, Lindahlsalen, Evolutionsbiologiskt centrum (EBC), Norbyvägen 18 A, Uppsala, 09:15 (English)
Available from: 2008-05-19 Created: 2008-05-19 Last updated: 2009-04-03Bibliographically approved

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