Emil Schüler1, Nils Rudqvist2, Toshima Z Parris3, Britta Langen2, Khalil Helou3, Eva Forssell-Aronsson2. 1. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: emil.schuler@gu.se. 2. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. 3. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Abstract
INTRODUCTION: The kidneys are one of the main dose limiting organs in (177)Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from (177)Lu-octreotate exposure. METHODS: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq (177)Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. RESULTS: Distinct transcriptional responses were observed following (177)Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. CONCLUSION: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues.
INTRODUCTION: The kidneys are one of the main dose limiting organs in (177)Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from (177)Lu-octreotate exposure. METHODS: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq (177)Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. RESULTS: Distinct transcriptional responses were observed following (177)Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. CONCLUSION: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues.
Authors: Nils Rudqvist; Johan Spetz; Emil Schüler; Toshima Z Parris; Britta Langen; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2015-07-15 Impact factor: 3.240
Authors: Emil Schüler; Maria Larsson; Toshima Z Parris; Martin E Johansson; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2015-08-19 Impact factor: 3.240
Authors: Shanaz A Ghandhi; Lubomir B Smilenov; Carl D Elliston; Mashkura Chowdhury; Sally A Amundson Journal: BMC Med Genomics Date: 2015-05-12 Impact factor: 3.063
Authors: Nils Rudqvist; Johan Spetz; Emil Schüler; Toshima Z Parris; Britta Langen; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2017-02-21 Impact factor: 3.240
Authors: An Aerts; Uta Eberlein; Sören Holm; Roland Hustinx; Mark Konijnenberg; Lidia Strigari; Fijs W B van Leeuwen; Gerhard Glatting; Michael Lassmann Journal: Eur J Nucl Med Mol Imaging Date: 2021-04-29 Impact factor: 9.236