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It has traditionally been attributed to radiation-induced salivary gland dysfunction; however, RRC often develops even when appropriate oral care is provided, including fluoride application and regular hygiene practices. This clinical inconsistency suggests that salivary dysfunction alone cannot fully explain the onset and severity of RRC. The direct physicochemical effects of radiation on the organic and inorganic components of dental hard tissues remain poorly understood. In this study, extracted human third molars were subjected to a clinical IMRT protocol, using either a single high dose (20\u00a0Gy\u2009\u00d7\u20091) or a fractionated regimen (2\u00a0Gy\/day\u2009\u00d7\u200935, total 70\u00a0Gy). We then evaluated radiation-induced changes in tooth structure by measuring Vickers microhardness, acid resistance (calcium elution), collagen degradation (autofluorescence), and internal dentin pH. Radiation exposure significantly altered enamel hardness: it increased after 20\u00a0Gy but decreased following 70\u00a0Gy. Calcium release increased in crown enamel (70\u00a0Gy) and root dentin (20\u00a0Gy), while decreasing in crown dentin (20\u00a0Gy). Autofluorescence imaging showed a significant reduction in dentinal collagen after fractionated exposure. Both groups exhibited an alkaline shift in dentin pH, more pronounced in the single-dose group. These findings provide physicochemical evidence for a non-salivary mechanism contributing to RRC. To effectively prevent RRC, additional strategies to reduce direct radiation damage to dental tissues may be necessary alongside conventional salivary-focused approaches.<\/jats:p>","DOI":"10.1007\/s00411-025-01180-w","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T12:06:19Z","timestamp":1765800379000},"page":"211-219","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct radiation damage to human tooth under IMRT for head and neck cancer: physicochemical evidence supporting a non-salivary mechanism for radiation-related caries"],"prefix":"10.1007","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-7094","authenticated-orcid":false,"given":"Toru","family":"Tamahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumu","family":"Kouketsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"issue":"6","key":"1180_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-021-06543-5","volume":"32","author":"DMG de Amorim","year":"2021","unstructured":"de Amorim DMG, Ver\u00edssimo AH, Ribeiro AKC, de Assun\u00e7\u00e3o ESRO, de Assun\u00e7\u00e3o IV, Caldas M, Borges BCD (2021) Effects of ionizing radiation on surface properties of current restorative dental materials. 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