Comparison of Coding Transcriptomes in Fibroblasts Irradiated With Low and High LET Proton Beams and Cobalt-60 Photons

Steffen Nielsen*, Niels Bassler, Leszek Grzanka, Louise Laursen, Jan Swakon, Pawel Olko, Christian Nicolaj Andreassen, Jan Alsner, Brita Singers Sørensen

*Corresponding author for this work

    Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

    Abstract

    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.
    Original languageEnglish
    JournalInternational Journal of Radiation Oncology Biology Physics
    Volume103
    Issue5
    Pages (from-to)1203-1211
    Number of pages9
    ISSN0360-3016
    DOIs
    Publication statusPublished - 2019

    Keywords

    • CANCER-CELLS
    • DIFFERENTIAL GENE-EXPRESSION
    • MAP3K8
    • PROFILE
    • RADIATION
    • RELATIVE BIOLOGICAL EFFECTIVENESS
    • THERAPY

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