Cyclophosphamide-Induced Morphological Changes in Dental Root Development of ICR Mice

Abstract

BackgroundSurvivors of childhood cancer are at risk of late dental development. Cyclophosphamide is one of the most commonly used chemotherapeutic agents against cancer in children. The aim of this study was 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.MethodsWe treated 16 12-day-old ICR mice 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. After scanning, 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. Histological changes in the apical region were then assessed via hematoxylin and eosin staining.ResultsThe mandibular molars of all experimental mice showed evidence of cytotoxic injury, which appeared in the form of anomalous root shapes. Although all roots developed further after cyclophosphamide injection, the 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 that of roots in the control group. In addition, hematoxylin and eosin staining of the distal roots in the experimental group showed increased dentin thickness in the apical region.ConclusionOur results suggest that cyclophosphamide can result in short root lengths and early apical foramen closure, eventually leading to V-shaped or thin roots.

Effects of oncological treatment on tooth development in children with brain tumors: Description of cases

“…have led to the disturbance in the length and shape of roots of the first molars in 12-day-old mice. 17 In our patients, brain tumors were surgically removed at the first stage of treatment. In some cases, surgery of head in cancer therapy may also lead to the disturbance in occlusion.…”

Surgical-Orthodontic Management of Mandibular Hypoplasia with Severely Short-Rooted Dentition Secondary to Anti-Leukemic Treatment: A Case Report

“…Consequently, the molar roots of these experimental rats developed significantly slower and shorter in length. Additionally, the apical foramen of those roots tended to close faster, forming anomalous root shapes [21][22][23]. Root resorption is a potential side effect of orthodontic therapy.…”

Evaluation of the Impacts of Chemotherapeutics on Odontogenesis Process: Findings from a Systematic Review

“…Among the eight articles assessed, five were studies using human models, two of them being studies of case reports, 32,33 one observational sectional study 34 and a longitudinal one 35 ; four of them were related to animal studies, all of them standardized laboratory tests. [36][37][38][39] The results found in each study were separated into two groups, the first one involving laboratory tests with animal models and the second one with human studies (►Tables 1, 2, 3, 4).…”

“…Also, interruption of cell cycle and loss of morphology and secretory activity; its ability to recover function and morphology appears to be less predictable with an increased dosage. 13,32,38 Observable later effects are: eruptive disorders, mesiodens, dentinomas, hypoplasia, taurodontia, root shortening, microdontia or agenesia of a tooth or group of teeth, more often present in patients submitted to high dose treatment protocols. 16,20,27,40 Adatia, 36 in his experiment with Wistar rats, observed histological changes in the organization, morphology, reproductive capacity, and a degree of cell regeneration, dividing the groups by different doses (40, 80 and 120 mg/kg) and by counting days after exposure (1, 4 and 8 days).…”