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Comparison of Coding Transcriptomes in Fibroblasts Irradiated With Low and High LET Proton Beams and Cobalt-60 Photons
Stockholm University, Faculty of Science, Department of Physics.
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Number of Authors: 92019 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 103, no 5, p. 1203-1211Article in journal (Refereed) Published
Abstract [en]

Purpose: To identify differential cellular responses after proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type. Methods and Materials: A panel of primary dermal fibroblast cultures was irradiated with low and higher linear energy transfer (LET) proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions of 3.5 Gy (relative biological effectiveness) using a relative biological effectiveness of 1.1 for proton doses. Cells were harvested 2 hours after the final fraction was delivered, and RNA was purified. RNA sequencing was performed using Illumina NextSeq 500 with high-output kit. The edgeR package in R was used for differential gene expression analysis. Results: Pairwise comparisons of the transcriptomes in the 3 treatment groups showed that there were 84 and 56 differentially expressed genes in the low LET group compared with the Cobalt-60 group and the higher LET group, respectively. The higher LET proton group and the Cobalt-60 group had the most distinct transcriptome profiles, with 725 differentially regulated genes. Differentially regulated canonical pathways and various regulatory factors involved in regulation of biological mechanisms such as inflammation, carcinogenesis, and cell cycle control were identified. Conclusions: Inflammatory regulators associated with the development of normal tissue complications and malignant transformation factors seem to be differentially regulated by higher LET proton and Cobalt-60 photon irradiation. The reported transcriptome differences could therefore influence the progression of adverse effects and the risk of developing secondary cancers.

Place, publisher, year, edition, pages
2019. Vol. 103, no 5, p. 1203-1211
National Category
Cancer and Oncology Physical Sciences
Research subject
Medical Radiation Physics
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URN: urn:nbn:se:su:diva-167566DOI: 10.1016/j.ijrobp.2018.11.065ISI: 000461048600030PubMedID: 30529373OAI: oai:DiVA.org:su-167566DiVA, id: diva2:1302962
Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-08Bibliographically approved

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Bassler, NielsGrzanka, LeszekSwakon, JanAlsner, JanSørensen, Brita Singers
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