Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation

Nielsen, Strange; Bassler, Niels; Grzanka, L.; Swakoń, Jan; Olko, P.; Andreassen, Christian Nicolaj; Overgaard, Jens; Alsner, Jan; Sørensen, Brita Singers

doi:10.1080/0284186x.2017.1351623

Cited by 19 publications

(22 citation statements)

References 29 publications

(36 reference statements)

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“…Various RBE values for endpoints other than cell survival have been measured in vitro, for example, induction of reactive oxygen species leading to oxidative stress, which regulates a variety of response pathways, DNA single or double-strand breaks, foci formation, repair proteins, gene expression, chromosome aberrations, mutations, micronuclei formation, apoptosis, and cell cycle effects (see eg, [43–46]). The majority of data support an average RBE of ~1.1.…”

Section: Rbe Variations In Laboratory Experimentsmentioning

confidence: 99%

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Paganetti

2018

International Journal of Particle Therapy

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Proton therapy treatments are prescribed using a biological effectiveness relative to photon therapy of 1.1, that is, proton beams are considered to be 10% more biologically effective. Debate is ongoing as to whether this practice needs to be revised. This short review summarizes current knowledge on relative biological effectiveness variations and uncertainties in vitro and in vivo. Clinical relevance is discussed and strategies toward biologically guided treatment planning are presented.

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Section: Rbe Variations In Laboratory Experimentsmentioning

confidence: 99%

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Paganetti

2018

International Journal of Particle Therapy

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“…The data are derived from material generated in a previous study, where qPCR data for other transcripts were reported. LET values presented here were reported in the previous study 7 .…”

Section: Resultsmentioning

confidence: 52%

“…Cobalt-60 beam irradiation was delivered using the Theratron 780E system with a 0.307 Gy/min dose rate. Additional set-up details are previously reported elsewhere 7 .…”

Section: Methodsmentioning

confidence: 99%

“…Previous research indicates that molecular mechanisms such as DNA repair and epigenetic regulation may be affected differently by various radiation qualities 2–6 . Furthermore, the transcriptional response may also be influenced by position in the proton beam as the linear energy transfer (LET) increases along the proton track 7 . Therefore, it seems unlikely that the differences in transcriptional response to photon and proton irradiation can be equated by modulating the radiation dose.…”

Section: Introductionmentioning

confidence: 99%

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Optimal reference genes for normalization of qPCR gene expression data from proton and photon irradiated dermal fibroblasts

Nielsen

Bassler

Grzanka

et al. 2018

Sci Rep

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The transcriptional response of cells exposed to proton radiation is not equivalent to the response induced by traditional photon beams. Changes in cellular signalling is most commonly studied using the method Quantitative polymerase chain reaction (qPCR). Stable reference genes must be used to accurately quantify target transcript expression. The study aim was to identify suitable reference genes for normalisation of gene expression levels in normal dermal fibroblasts irradiated with either proton or photon beams. The online tool RefFinder was used to analyse and identify the most stably expressed genes from a panel of 22 gene candidates. To assess the reliability of the identified reference genes, a selection of the most and least stable reference genes was used to normalise target transcripts of interest. Fold change levels varied considerably depending on the used reference gene. The top ranked genes IPO8, PUM1, MRPL19 and PSMC4 produced highly similar target gene expression, while expression using the worst ranked genes, TFRC and HPRT1, was clearly modified due to reference gene instability.

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“…For example, faster production of reactive oxygen species [18] and enhanced levels of cell apoptosis [19] were identified after irradiation with low linear energy transfer (LET) proton irradiation in comparison to photon irradiation. Furthermore, differential gene expression in response to the 2 modalities of irradiation and increasing RBEs of cell killing along the axis of an SOBP also suggest different mechanisms being induced by photon and proton irradiation, which could be exploited as part of a combined treatment modality [20,21]. These preclinical insights contrast with the generic constant RBE of 1.1 still applied in clinical practice [13,22].…”

Section: Differential Biological Responses To Photon and Proton Irradmentioning

confidence: 99%

Combined Treatment Modalities for High-Energy Proton Irradiation: Exploiting Specific DNA Repair Dependencies

Deycmar

Pruschy

2018

International Journal of Particle Therapy

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DNA repair deficiencies and genome instability are common features and hallmarks of cancer and are ubiquitously found in the full spectrum of malignant diseases. Heritable DNA repair deficiencies, for example, due to BRCA1 and BRCA2 mutations, and subsequent loss of heterozygosity in mammary, ovarian, and prostate carcinoma, are risk factors for the early development of cancer. Despite their detrimental role in tumorigenesis, these deficiencies also provide novel opportunities for treatment options. Current and future pharmacologic approaches in medical oncology rely on the exploitation of such genetically defined, tumor-specific Achilles' heels and integrate the genetic background of a tumor into the treatment strategy. For example, homologous recombination-corrupted, BRCA1/2-mutated tumors are becoming hypersensitive to inhibitors of an additional DNA-damage-repair mechanism and are successfully treated with respective molecular targeting agents such as PARP1 inhibitors. Patient stratification in radiation oncology today is primarily based on clinical parameters and uses highly sophisticated diagnostic imaging for treatment planning on the individual level. Radiation oncology only minimally takes the genetic makeup of tumors into account, and little attention has been given to the fact that the different modalities of ionizing radiation, such as photon and proton irradiation, may also induce differential damages and biological processes, which might again be influenced by the genetic makeup and mutational status of the tumor. However, radiation oncology is nowadays challenged to understand subtle differences induced by the different qualities of ionizing radiation, and to efficiently exploit and to integrate these differential responses in a personalized treatment approach alone and as part of combined treatment modalities with pharmacologic agents. Here we will review recent insights on the differential DNA damage responses to photon and proton irradiation and discuss their implications for combined treatment modalities with chemotherapeutical agents and small molecular targeting compounds.

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Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation

Cited by 19 publications

References 29 publications

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Optimal reference genes for normalization of qPCR gene expression data from proton and photon irradiated dermal fibroblasts

Combined Treatment Modalities for High-Energy Proton Irradiation: Exploiting Specific DNA Repair Dependencies

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