Abstract Aim: Radiation therapy to treat oral cancer introduces various harms, including decreased hardness of dentin and enamel. Fluoride treatments, including silver diamine fluoride (SDF), have been used as a tool to combat these harms, but its influences on the thermal properties of dentin and enamel prior to and after radiation therapy are not well understood. Thus, this study analyzed how SDF influences the thermal stability of dentin and enamel that has been exposed to radiation therapy intended for head and neck cancer patients. Methods: Forty human posterior teeth were collected, cleaned of debris and soft tissue, and then mounted into acrylic resin molds. The teeth were divided into two equal groups, with one group being the control (no treatment) and the other group receiving SDF treatment. Using an X-Rad 320ix biological irradiator, all teeth were subjected to two grays of radiation therapy every day for six weeks. Afterwards, the dentin and enamel were pulverized a SPEX freezer mill. Samples were heated in a NETZSCH Thermal Analysis instrument, and the amount of carbon dioxide and water released was determined. All teeth were heated to 1429 °C from room temperature. Results: The SDF-treated dentin released the most carbon dioxide (49,611.82 ppm/mg), followed by irradiated dentin (47,672.76 ppm/mg) and untreated dentin (45,249.66 ppm/mg). In contrast, the SDF-treated enamel released less carbon dioxide (7,367.62 ppm/mg) than the control enamel (8,172.01 ppm/mg). The pattern of release of water was different from that of carbon dioxide. The control dentin group released the most water (45.56 ppt/mg), followed by the SDF-treated (39.72 ppt/mg) and irradiated dentin (23.51 ppt/mg). Similarly, the control enamel also released the highest amount of water (0.83 ppt/mg), as well as the highest amount of carbon dioxide. The SDF-treated enamel released around 65% of the water compared to the control enamel group (0.54 ppt/mg). Furthermore, the irradiated dentin had the largest heat reversal temperatures for carbon dioxide (85.19 °C) and water (86.57 °C). Conclusions: The impacts of SDF treatment and radiation vary between dentin and enamel. Comparatively, dentin has a higher content of combustible material than enamel. Radiation treatment reduces the water content of both enamel and dentin, which may make teeth more susceptible to fracture. Therefore, regular dental check-ups and frequent fluoride treatment to increase the strength of the teeth are recommended for patients undergoing radiation therapy. Citation Format: Rachel J. Kulchar, Yusuke Kakiuchi, Vania Sanchez-Gamarra, Jie Deng, Francis Mante. Fluoride effects on thermal properties of irradiated dentin and enamel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6035.