Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

: Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig’s epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon. formation, no morphological changes in the crown were observed in the molars, irrespective of CPA dosages. These find ings are consistent with a recent report that nondividing columnar od-ontoblasts and ameloblasts in the mice incisor were not affected by CPA administration 29) . Delayed tooth eruption is well-known as a long-term side effects of chemotherapy 27) . Tooth eruption is a complex and tightly regulated process that is divided into five stages; preeruptive move-ments, intraosseous stage, mucosal penetration, preocclusal and post oc-clusal stages 30) Delayed tooth is caused by impairment of the pre-eruptive movement in eruptive stages. CPA administration did not influence the of during the process of tooth