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, HERSOIa cells showed decreases in E-cadherin expression, while N-cadheiin 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.