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Urinary Thymidine Dimer as a Marker of Total BodyBurden of UV-Inflicted DNA Damage in Humans
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (genetisk toxikologi)
2005 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, no 12, 2868-2872 p.Article in journal (Refereed) Published
Abstract [en]

High levels of DNA damage are induced in human skin following exposure to UV radiation. Cyclobutane thymidine dimer (T = T) is the most common of these lesions, which are enzymatically removed as oligonucleotides from DNA and further degraded before excretion in urine. Analysis of such repair products in the urine could serve as a biomarker of total body burden of UV exposure. The aim of this study was to examine the kinetics of T = T excretion following a single tanning session in a commercial solarium and to validate the method by delivering different doses. Ten individuals used the solarium for a total of 35 sessions of body tanning. Urine was collected before UV exposure and daily thereafter (up to 5 or 11 days) and T = T was analyzed using a very sensitive and quantitative P-32-postlabeling technique combined with high-performance liquid chromatography. Following exposure, T = T levels increased dramatically and reached a peak 3 days later; afterwards, the T = T levels gradually decreased. The total amount of T = T excreted differed about 5-fold among subjects given an equal dose. A 50% excretion time was calculated using the excretion data for the first 5 days and it was found to be between 55 and 76 hours for different individuals. There was a good correlation between the amount of T = T excreted during days 1 to 5 and the delivered UV dose. Reducing exposure time to 50% lowered the amount of T = T to 47%; if half of the lamps were covered, T = T decreased to 44%. Our data show that urinary T = T could be a suitable noninvasive biomarker for UV exposure; a finding which could also be applicable to studies in children.

Place, publisher, year, edition, pages
2005. Vol. 14, no 12, 2868-2872 p.
Keyword [en]
CYCLOBUTANE PYRIMIDINE DIMERS; THYMINE DIMERS; SKIN-CANCER; REPAIR; 8-OXO-2'-DEOXYGUANOSINE; SUNLIGHT; SUN
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-45906DOI: 10.1158/1055-9965.EPI-05-0164OAI: oai:DiVA.org:su-45906DiVA: diva2:370299
Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Biomarkers for DNA damage in human biomonitoring
Open this publication in new window or tab >>Biomarkers for DNA damage in human biomonitoring
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genomic DNA in humans is constantly exposed to different kinds of damage. Therefore, it is desirable to implement methods for detecting and measuring of inflicted body burden. Human biomonitoring (HBM) can here be a useful tool as a link between environmental exposure and disease outcome. The present thesis aims to monitor DNA damage in humans by studies on: 1) urinary thymidine dimer (T=T) as a novel biomarker (BM) of human exposure to UV-light; 2) enumeration of variants in HPRT gene in human peripheral blood lymphocytes by developing a sensitive flow cytometric (FCM) analysis; 3) the impact of dietary habits on genomic stability in vegetarians and omnivores in terms of micronuclei (MN) induction detected by FCM. Urinary T=T was quantified by a 32P-postlabeling technique, the kinetics of T=T excretion was studied and the method was validated by delivering controlled UV-doses. The major conclusion was that the amount of urinary T=T was determined by the UV dose, and hence T=T can be used as a BM of UV exposure. Moreover, a new approach for rapid and sensitive enumeration of HPRT-variants by FCM was developed. The obtained HPRT-frequencies were comparable to those previously published by others. Finally, the FCM assay for MN enumeration was applied to study effects of dietary habits in vegetarians and omnivores. The main finding was that vegetarians had significantly lower MN frequencies compared to omnivores. In summary, the applied BMs and respective methods have high sensitivity and/or throughput possibility which are important factors considered in HBM.

 

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2010. 55 p.
Keyword
biomonitoring, biomarkers, DNA damage, cancer, diet, UV-light
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-45910 (URN)978-91-7447-183-0 (ISBN)
Public defence
2010-12-17, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20C, Stockholm, 14:00 (English)
Opponent
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Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manscript.Available from: 2010-11-25 Created: 2010-11-16 Last updated: 2010-11-16Bibliographically approved

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