A Step Toward Personalized Cancer Treatment Simultaneous Detection of Multiple Types of Chemotherapyinduced DNA Damage Using Single Molecule Imaging

dc.contributor.authorFoss, Ebba
dc.contributor.departmentChalmers tekniska högskola / Institutionen för biologi och biotekniksv
dc.contributor.departmentChalmers University of Technology / Department of Biology and Biological Engineeringen
dc.contributor.examinerWesterlund, Fredrik
dc.contributor.supervisorAkwasi Aning, Obed
dc.date.accessioned2022-11-15T14:59:00Z
dc.date.available2022-11-15T14:59:00Z
dc.date.issued2022
dc.date.submitted2020
dc.description.abstractChemotherapy is commonly used to treat cancer today, either alone or more commonly as part of combination therapy. Response to a certain chemotherapeutic agent is highly individual, both in terms of treatment efficacy and the extent to which healthy cells are affected. For several drugs, induced DNA damage provides the main cytotoxic effect, and a method for evaluating this damage could therefore prove a powerful tool in treatment planning. In this thesis, a single molecule imaging approach is used to assess chemotherapy-induced DNA damage, allowing visualisation of damage sites on individual DNA strands. While previous studies have focused on one damage type, or collective damage without distinction between types, a novel modification to pre-existing techniques that allows for this distinction has recently been demonstrated. In this thesis, the alkylating agent temozolomide was used to illustrate how different damage types can be distinguished with a single molecule imaging approach. This is done using repair enzymes associated with different DNA repair pathways. The repair enzymes sequentially incorporate spectrally distinct fluorescent nucleotides at the damage site which are then visualized as fluorescent spots of two different colours on individual DNA molecules. This distinction could be shown with high repeatability in terms of colour ratio. While both enzymes used separately clearly repaired the treated DNA, there appeared to be an overlap when applying them sequentially. This could suggest a problem with enzyme specificity. Further exploration of this issue is needed to verify the feasibility of single molecule imaging for the purpose of simultaneous detection of chemotherapy-induced DNA damage types.
dc.identifier.coursecodeBBTX03
dc.identifier.urihttps://odr.chalmers.se/handle/20.500.12380/305811
dc.language.isoeng
dc.setspec.uppsokLifeEarthScience
dc.subjectDNA damage
dc.subjectSingle Molecule Imaging
dc.subjectChemotherapy
dc.subjectTemozolomide
dc.subjectSimultaneous Labelling
dc.subjectDNA alkylation
dc.titleA Step Toward Personalized Cancer Treatment Simultaneous Detection of Multiple Types of Chemotherapyinduced DNA Damage Using Single Molecule Imaging
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster's Thesisen
dc.type.uppsokH
local.programmeBiotechnology (MPBIO), MSc
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