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Furan is not genotoxic in the micronucleus assay in vivo or in vitro
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
2007 (English)In: Toxicology Letters, ISSN 0378-4274, Vol. 169, no 1, 43-50 p.Article in journal (Refereed) Published
Abstract [en]

Furan, a potential human carcinogen, is formed during heat-treatment of food. Previous studies of the genotoxicity of furan have given disparate results. Hence, there is a need for complementary data to clarify the mechanism behind the carcinogenicity of furan. In this study, we have used the flow cytometer-based micronucleus assay in mice and the cytokinesis-block micronucleus assay in human lymphocytes to investigate the genotoxic potential of furan. Three in vivo experiments were performed: intraperitoneal or subcutaneous injection of furan in male Balb/C mice (0–300 and 0–275 mg/kg body weight, respectively) and intraperitoneal injection of male CBA mice (0 and 225 mg/kg body weight). No increased level of micronucleated erythrocytes was detected in any of the in vivo experiments. In the in vitro setup, human lymphocytes from two donors were treated with furan in concentrations from 0 to 100 mM, either with or without metabolic activation (liver homogenate from rat). In parity with the in vivo results there was no significant increase in the frequency of micronucleated cells here either. As neither the in vivo nor the in vitro studies disclose any significant increase in the micronucleus frequency after treatment with furan, our results support that the carcinogenicity of furan is caused by a non-genotoxic mechanism.

Place, publisher, year, edition, pages
2007. Vol. 169, no 1, 43-50 p.
Keyword [en]
Furan, Micronucleus assay, Flow cytometer, Chromosome aberration
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-97343DOI: 10.1016/j.toxlet.2006.08.020OAI: oai:DiVA.org:uu-97343DiVA: diva2:172236
Available from: 2008-05-19 Created: 2008-05-19 Last updated: 2010-02-11Bibliographically 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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