ArticleRadiation and environmental biophysics2018
Biodosimetric transcriptional and proteomic changes are conserved in irradiated human tissue.
Article in Radiation and environmental biophysics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Modelling aggressive prostate cancers of young men in immune-competent mice, driven by isogenic Trp53 alterations and Pten loss.Cell death & disease · 2022Article
- Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype: a case report.BMC urology · 2020Article
- High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot.Journal for immunotherapy of cancer · 2020Article
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11 authors.
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Abstract
Transcriptional dosimetry is an emergent field of radiobiology aimed at developing robust methods for detecting and quantifying absorbed doses using radiation-induced fluctuations in gene expression. A combination of RNA sequencing, array-based and quantitative PCR transcriptomics in cellular, murine and various ex vivo human models has led to a comprehensive description of a fundamental set of genes with demonstrable dosimetric qualities. However, these are yet to be validated in human tissue due to the scarcity of in situ-irradiated source material. This represents a major hurdle to the continued development of transcriptional dosimetry. In this study, we present a novel evaluation of a previously reported set of dosimetric genes in human tissue exposed to a large therapeutic dose of radiation. To do this, we evaluated the quantitative changes of a set of dosimetric transcripts consisting of FDXR, BAX, BCL2, CDKN1A, DDB2, BBC3, GADD45A, GDF15, MDM2, SERPINE1, TNFRSF10B, PLK3, SESN2 and VWCE in guided pre- and post-radiation (2 weeks) prostate cancer biopsies from seven patients. We confirmed the prolonged dose-responsivity of most of these transcripts in in situ-irradiated tissue. BCL2, GDF15, and to some extent TNFRSF10B, were markedly unreliable single markers of radiation exposure. Nevertheless, as a full set, these genes reliably segregated non-irradiated and irradiated tissues and predicted radiation absorption on a patient-specific basis. We also confirmed changes in the translated protein product for a small subset of these dosimeters. This study provides the first confirmatory evidence of an existing dosimetric gene set in less-accessible tissues-ensuring peripheral responses reflect tissue-specific effects. Further work will be required to determine if these changes are conserved in different tissue types, post-radiation times and doses.
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