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The improved precision of radiation dose delivery of recent technological developments in radiotherapy has the potential to reduce the radiation dose to organ regions that contribute the most to the development of side effects. This review discusses the contribution of regional variation in radiation responses in several organs. In the brain, various regions were found to contribute to radiation-induced neurocognitive dysfunction. In the parotid gland, the region containing the major ducts was found to be critical in hyposalivation. The heart and lung were each found to exhibit regional responses while also mutually affecting each other\u2019s response to radiation. Sub-structures critical for the development of side effects were identified in the pancreas and bladder. The presence of these regional responses is based on a non-uniform distribution of target cells or sub-structures critical for organ function. These characteristics are common to most organs in the body and we therefore hypothesize that regional responses in radiation-induced normal tissue damage may be a shared occurrence. Further investigations will offer new opportunities to reduce normal tissue side effects of radiotherapy using modern and high-precision technologies.<\/jats:p>","DOI":"10.3390\/cancers13030367","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T12:16:18Z","timestamp":1611144978000},"page":"367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Regional Responses in Radiation-Induced Normal Tissue Damage"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7370-0338","authenticated-orcid":false,"given":"Dani\u00eblle C.","family":"Voshart","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department of Biomedical Sciences of Cells &amp; Systems\u2013Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wiedemann","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department of Biomedical Sciences of Cells &amp; Systems\u2013Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-1234","authenticated-orcid":false,"given":"Peter","family":"van Luijk","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department of Biomedical Sciences of Cells &amp; Systems\u2013Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Barazzuol","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department of Biomedical Sciences of Cells &amp; Systems\u2013Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/cncr.21324","article-title":"The Role of Radiotherapy in Cancer Treatment","volume":"104","author":"Delaney","year":"2005","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-019-0064-5","article-title":"Radiotherapy Toxicity","volume":"5","author":"Niedermann","year":"2019","journal-title":"Nat. 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