Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers

Autor: Antoine Laval, Grzegorz Woźniak, Navita Somaiah, Piotr Widlak, Lucyna Ponge, Ellen M. Donovan, Grainne O’Brien, Leszek Miszczyk, Lone Gothard, Serge M. Candéias, Isabelle Testard, Elizabeth A. Ainsbury, Christophe Badie, Lourdes Cruz-Garcia, Sue Boyle
Přispěvatelé: Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], Centre for Vision, Speech and Signal Processing (CVSSP), University of Surrey (UNIS), Institute for Cancer Research/Royal Marsden NHS Foundation Trust, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
Lipopolysaccharides
Male
Curcumin
Epidemiology
Cyclin G1
Health
Toxicology and Mutagenesis
[SDV.CAN]Life Sciences [q-bio]/Cancer
Antineoplastic Agents
Pharmacology
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Neoplasms
Gene expression
Medicine
Humans
Radiology
Nuclear Medicine and imaging
Transcription factor
Aged
Regulation of gene expression
Aged
80 and over
business.industry
Confounding
Cancer
Radiotherapy Dosage
Middle Aged
medicine.disease
Phosphoric Monoester Hydrolases
3. Good health
Gene Expression Regulation
Neoplastic
030104 developmental biology
chemistry
13. Climate action
030220 oncology & carcinogenesis
Case-Control Studies
Female
Radiotherapy
Intensity-Modulated
business
Ex vivo
Biomarkers
Zdroj: Health Physics
Health Physics, Lippincott, Williams & Wilkins, 2018, 115 (1), pp.90-101. ⟨10.1097/HP.0000000000000844⟩
Health Physics, 2018, 115 (1), pp.90-101. ⟨10.1097/HP.0000000000000844⟩
ISSN: 1538-5159
0017-9078
DOI: 10.1097/HP.0000000000000844⟩
Popis: International audience; For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose- and time-dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes.
Databáze: OpenAIRE
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