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The impact of folate status and folic acid supplementation on the micronucleus frequency in human erythrocytes
National Food Administration, Uppsala.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
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2006 (English)In: Mutation Research, ISSN 1383-5742, Vol. 603, no 1, 33-40 p.Article in journal (Refereed) Published
Abstract [en]

Folic acid has a well-documented stabilising effect on chromosomes. A correlation between folate status and chromosome stability in humans has been reported in studies that were restricted to certain subpopulations, e.g., folate-deficient persons. The goal of the present investigation was to clarify if there also is a correlation between folate status and chromosome stability among individuals without any folate deficiency.

The method used here is the recently developed flow cytometry-based micronucleus assay in human transferrin-positive reticulocytes (MN-Trf-Ret). In a blood sample, separation of the very young reticulocytes from the mature erythrocytes makes this micronucleus assay possible.

This investigation comprises three studies (cross-sectional, giving baseline data), two of which are connected to an intervention study. In the three cross-sectional studies (total number of subjects, 99) the frequency of MN-Trf-Ret (fMN-Trf-Ret) was measured and compared with the serum folate status. In two of the studies also serum homocysteine and Vitamin B12 were measured and compared with the baseline fMN-Trf-Ret. Combining the results from the three cross-sectional studies, a negative correlation between folate status and fMN-Trf-Ret was obtained (p < 0.05).

The goal of the intervention studies was to clarify if different nutritional supplementations had any effect on the fMN-Trf-Ret and the cell proliferation (percentage polychromatic erythrocytes, PCE). Each of the two studies involved two groups, one placebo and one supplemented group. In one of the studies the supplementation was folic acid, 1000 μg/day during 1 week (n = 30, both sexes); in the other intervention study, folic acid (800 μg/day), B12 (20 μg/day) and B6 (4 mg/day) were taken during 1 week (n = 29, both sexes). No significant difference in %PCE or fMN-Trf-Ret between the two groups was found in either of the two intervention studies.

Place, publisher, year, edition, pages
2006. Vol. 603, no 1, 33-40 p.
Keyword [en]
Folic acid, Folate, Micronucleus, Flow cytometer, Human erythrocytes, Human reticulocytes, Vitamin B12, Homocysteine
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97345DOI: 10.1016/j.mrgentox.2005.10.009PubMedID: 16386942OAI: oai:DiVA.org:uu-97345DiVA: diva2:172238
Available from: 2008-05-19 Created: 2008-05-19 Last updated: 2010-12-27Bibliographically 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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