title: Effect of the antineoplastic agent busulfan on rat molar root development.
abstract: OBJECTIVE
  The antineoplastic bifunctional-alkylating agent busulfan (Bu) induces developmental anomalies. We examined histopathological changes in the molar roots of rats that received Bu at different stages of root formation.
  
  
  METHODS
  At different developmental stages, i.e., on postnatal days (P) 13, 15, and 19, rats were administered 7.5 mg/kg of Bu dissolved in dimethyl sulfoxide (DMSO) and then killed on P 30. After micro-computed tomography analysis, the maxillary first molars underwent immunohistochemical analysis for cytokeratin 14 (CK14), nestin, and dentin sialoprotein (Dsp). This was followed by histomorphometric analysis.
  
  
  RESULTS
  The rats receiving Bu at an early stage (i.e., P 13 and P 15) showed osteodentin formation and complete destruction of the Hertwig's epithelial root sheath (HERS). Cells around osteodentin showed nestin and Dsp immunoreactivity. The root lengths in rats treated with Bu at P 13 (1228.44 ± 62.17 μm) and P 15 (1536.08 ± 109.71 μm) were lower than that in the control rats (1674.10 ± 40 μm). A narrowed apical foramen and an increased amount of osteodentin were also present, depending on the rat's age at the time of treatment (P < 0.05).
  
  
  CONCLUSIONS
  Busulfan treatment in juvenile rats resulted in abnormal root development, depending on the stage at which Bu was administered. This abnormal development may result from the destruction of the HERS. The administration of Bu caused a shortage of HERS cells, which are required for normal root development. This disturbs root formation, resulting in osteodentin formation and a narrowed apex foramen.
authors.forename: T
authors.initials: T
authors.lastname: Mitomi
authors.forename: Y
authors.initials: Y
authors.lastname: Kawano
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita-Kawano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002066:Busulfan / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000032:analysis; D008297:Male; D008963:Molar / Q000187:drug effects / Q000254:growth & development*; D064231:Nestin / Q000032:analysis; D009805:Odontogenesis / Q000187:drug effects* / Q000502:physiology; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000032:analysis; D014092:Tooth Root / Q000187:drug effects / Q000254:growth & development*; D055114:X-Ray Microtomography; D000099311:Dentin Sialophosphoprotein
chemical_list: D000970:Antineoplastic Agents; D002066:Busulfan; D016326:Extracellular Matrix Proteins; D053547:Keratin-14; D064231:Nestin; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein