Biomarkers for DNA damage in human biomonitoring
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
biomonitoring, biomarkers, DNA damage, cancer, diet, UV-light
Research subject Molecular Genetics
IdentifiersURN: urn:nbn:se:su:diva-45910ISBN: 978-91-7447-183-0OAI: oai:DiVA.org:su-45910DiVA: diva2:370314
2010-12-17, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20C, Stockholm, 14:00 (English)
Ljungman, Mats, Associate Professor
Jenssen, Dag, ProfessorGrawé, Jan, DoctorAbramsson-Zetterberg, Lilianne, Doctor
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manscript.2010-11-252010-11-162010-11-16Bibliographically approved
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