Tags

Type your tag names separated by a space and hit enter

Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells.
Int J Radiat Oncol Biol Phys 2018; 102(5):1577-1589IJ

Abstract

PURPOSE

Oral mucositis is one of the most prevalent side effects in patients undergoing radiation therapy for head and neck cancers. Current therapeutic agents such as palifermin recombinant human keratinocyte growth factor and amifostine do not efficiently or fully prevent mucositis. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study aimed to investigate the efficacy of DMSO in a clinically relevant mouse model of acute, radiation-induced oral mucositis.

METHODS AND MATERIALS

Oral mucositis was induced by a high single and fractioned irradiation of the head and neck area in C57BL/6J mice, and the effects of DMSO (by intraperitoneal injection) were assessed by macroscopic and histopathological examination. Epithelial stem and progenitor cells were analyzed by immunohistochemical staining of p63 and Ki-67, and DNA double-strand breaks (DSBs) were visualized by immunofluorescence detection of γ-H2AX. Tumor xenograft was obtained using CAL-27 cells.

RESULTS

Pretreatment with DMSO protected the oral mucosa from severe acute radiation injury, reduced the extent of radiation-induced weight loss, and had no significant effects on tumor weight in irradiated or nonirradiated xenograft mice. Furthermore, the efficacy of DMSO was superior to that of recombinant human keratinocyte growth factor and amifostine. DMSO treatment prevented the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation. More interestingly, the average levels of γ-H2AX foci were significantly decreased in p63-positive epithelial stem cells at 6 hours, but not at 2 hours, after irradiation, indicating that DMSO facilitated DNA DSB repair rather than suppressing the indirect action of irradiation.

CONCLUSIONS

DMSO prevents the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation by facilitating DNA DSB repair, thereby protecting against radiation-induced mucositis without tumor protection. Given its high efficacy and low toxicity, DMSO could be a potential treatment option to prevent radiation-induced oral mucositis.

Authors+Show Affiliations

School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, PR China; Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.Department of Gastroenterology, Hospital of Tsinghua Changgung, Beijing, PR China.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China.School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, PR China; Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing, PR China. Electronic address: zhoupk@bmi.ac.cn.Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory for Radiobiology, Beijing, PR China. Electronic address: congyw@nic.bmi.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30092334

Citation

Yang, Chao, et al. "Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells." International Journal of Radiation Oncology, Biology, Physics, vol. 102, no. 5, 2018, pp. 1577-1589.
Yang C, Tang H, Wang L, et al. Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells. Int J Radiat Oncol Biol Phys. 2018;102(5):1577-1589.
Yang, C., Tang, H., Wang, L., Peng, R., Bai, F., Shan, Y., ... Cong, Y. (2018). Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells. International Journal of Radiation Oncology, Biology, Physics, 102(5), pp. 1577-1589. doi:10.1016/j.ijrobp.2018.07.2010.
Yang C, et al. Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells. Int J Radiat Oncol Biol Phys. 2018 12 1;102(5):1577-1589. PubMed PMID: 30092334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells. AU - Yang,Chao, AU - Tang,Hongwei, AU - Wang,Limei, AU - Peng,Renjun, AU - Bai,Fan, AU - Shan,Yajun, AU - Yu,Zuyin, AU - Zhou,Pingkun, AU - Cong,Yuwen, Y1 - 2018/08/06/ PY - 2018/04/14/received PY - 2018/07/20/revised PY - 2018/07/23/accepted PY - 2018/8/10/pubmed PY - 2019/5/28/medline PY - 2018/8/10/entrez SP - 1577 EP - 1589 JF - International journal of radiation oncology, biology, physics JO - Int. J. Radiat. Oncol. Biol. Phys. VL - 102 IS - 5 N2 - PURPOSE: Oral mucositis is one of the most prevalent side effects in patients undergoing radiation therapy for head and neck cancers. Current therapeutic agents such as palifermin recombinant human keratinocyte growth factor and amifostine do not efficiently or fully prevent mucositis. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study aimed to investigate the efficacy of DMSO in a clinically relevant mouse model of acute, radiation-induced oral mucositis. METHODS AND MATERIALS: Oral mucositis was induced by a high single and fractioned irradiation of the head and neck area in C57BL/6J mice, and the effects of DMSO (by intraperitoneal injection) were assessed by macroscopic and histopathological examination. Epithelial stem and progenitor cells were analyzed by immunohistochemical staining of p63 and Ki-67, and DNA double-strand breaks (DSBs) were visualized by immunofluorescence detection of γ-H2AX. Tumor xenograft was obtained using CAL-27 cells. RESULTS: Pretreatment with DMSO protected the oral mucosa from severe acute radiation injury, reduced the extent of radiation-induced weight loss, and had no significant effects on tumor weight in irradiated or nonirradiated xenograft mice. Furthermore, the efficacy of DMSO was superior to that of recombinant human keratinocyte growth factor and amifostine. DMSO treatment prevented the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation. More interestingly, the average levels of γ-H2AX foci were significantly decreased in p63-positive epithelial stem cells at 6 hours, but not at 2 hours, after irradiation, indicating that DMSO facilitated DNA DSB repair rather than suppressing the indirect action of irradiation. CONCLUSIONS: DMSO prevents the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation by facilitating DNA DSB repair, thereby protecting against radiation-induced mucositis without tumor protection. Given its high efficacy and low toxicity, DMSO could be a potential treatment option to prevent radiation-induced oral mucositis. SN - 1879-355X UR - https://www.unboundmedicine.com/medline/citation/30092334/Dimethyl_Sulfoxide_Prevents_Radiation_Induced_Oral_Mucositis_Through_Facilitating_DNA_Double_Strand_Break_Repair_in_Epithelial_Stem_Cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0360-3016(18)33467-9 DB - PRIME DP - Unbound Medicine ER -