Cyclophosphamide-Induced Morphological Changes in Molar Roots of ICR Mice

Objectives: Survivors of childhood cancer are at a risk of late dental development. Cyclophosphamide is one of the most commonly used chemotherapeutic agents against cancer in children. This study aimed to investigate the effects of cyclophosphamide on root formation in the molars of growing mice, and to assess the morphological changes in these roots using three-dimensional structural images.
Methods: We treated 12-day-old ICR mice (CY; n = 16) with cyclophosphamide (100 mg/kg, i.p.) and 16 control mice with saline. At 16, 20, 24, and 27 days of age, the mandibular left first molars were scanned using soft micro-computed tomography; the structural indices were calculated using a three-dimensional image analysis system, and the images were subjected to three-dimensional reconstruction. The length and apical foramen area of all distal roots were assessed. To observe the state of the odontoblasts and root formation, we measured the root length and odontoblast number on the distal side of the distal root in HE-stained sections.
Results: Three-dimensional structural images showed that the roots in the experimental group tended to develop more slowly and were shorter than those in the control group. At 27 days of age, the mean root length was shorter in the experimental group than in the control group. Conversely, the apical foramen of the roots in the experimental group tended to close faster than those of roots in the control group. In addition, HE-stained sections showed that the mean root length in the CY group was significantly shorter than that of the control group, and the mean odontoblast number of the total distal roots in the CY group was lower than that in the control group.
Conclusions: Our results suggest that cyclophosphamide can result in short root length and early apical foramen closure, eventually leading to the formation of V-shaped or thin roots.