DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy
-
- Magy Sallam
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
-
- Mohamed Mysara
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
-
- Mohammed Benotmane
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
-
- Radia Tamarat
- Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LR2I, 92260 Fontenay-aux-Roses, France
-
- Susana Constantino Rosa Santos
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Lisbon School of Medicine of the Universidade de Lisboa, 1649-028 Lisbon, Portugal
-
- Daan Spoor
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
-
- Filip Van Nieuwerburgh
- Laboratory of Pharmaceutical Biotechnology, Ghent University, 9000 Ghent, Belgium
-
- Dieter Deforce
- Laboratory of Pharmaceutical Biotechnology, Ghent University, 9000 Ghent, Belgium
-
- Sarah Baatout
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
-
- Pieter-Jan Guns
- Laboratory of Physiopharmacology, University of Antwerp, 2610 Wilrijk, Belgium
-
- An Aerts
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
-
- Raghda Ramadan
- Radiobiology Unit, Interdisciplinary Biosciences, Belgian Nuclear Research Centre, SCK CEN, 2400 Mol, Belgium
抄録
<jats:p>Radiation-Induced CardioVascular Disease (RICVD) is an important concern in thoracic radiotherapy with complex underlying pathophysiology. Recently, we proposed DNA methylation as a possible mechanism contributing to RICVD. The current study investigates DNA methylation in heart-irradiated rats and radiotherapy-treated breast cancer (BC) patients. Rats received fractionated whole heart X-irradiation (0, 0.92, 6.9 and 27.6 Gy total doses) and blood was collected after 1.5, 3, 7 and 12 months. Global and gene-specific methylation of the samples were evaluated; and gene expression of selected differentially methylated regions (DMRs) was validated in rat and BC patient blood. In rats receiving an absorbed dose of 27.6 Gy, DNA methylation alterations were detected up to 7 months with differential expression of cardiac-relevant DMRs. Of those, SLMAP showed increased expression at 1.5 months, which correlated with hypomethylation. Furthermore, E2F6 inversely correlated with a decreased global longitudinal strain. In BC patients, E2F6 and SLMAP exhibited differential expression directly and 6 months after radiotherapy, respectively. This study describes a systemic radiation fingerprint at the DNA methylation level, elucidating a possible association of DNA methylation to RICVD pathophysiology, to be validated in future mechanistic studies.</jats:p>
収録刊行物
-
- International Journal of Molecular Sciences
-
International Journal of Molecular Sciences 23 (24), 16214-, 2022-12-19
MDPI AG