N-methyl-N-nitrosourea-induced changes in epithelial rests of Malassez and the development of odontomas in rats.

Morphological changes in the epithelial rests of Malassez (ERM) and the development of odontogenic tumors in the molars of female Lewis rats treated at 4 weeks of age with a single intraperitoneal injection of 50 mg/kg of N-methyl-N-nitrosourea (MNU) were examined at 12, 18 and 30 weeks of age. Following MNU exposure, the total number and average area of ERM in the cervical and furcational regions of the first, second and third molars of the mandible and maxilla were compared with age-matched control animals. The number of ERM at each time point was significantly greater in the MNU-treated group compared to the control group, but there was no time-dependent increase in the number of ERM in either group. The area of ERM was significantly larger in the MNU-treated group compared to the control group at each time point, and it increased in a time-dependent manner in the MNU-treated group. No increases in the number or area of ERM were observed in the control group. At 30 weeks of age, 23% of the MNU-treated rats had developed odontomas (complex type) in the molar region as well as in the incisor region. Immunohistochemically, the expression of tyrosine receptor kinase A (TrkA) and cytokeratin 14 (CK14) decreased, whereas p63 expression remained high during ERM enlargement. In tumors, ameloblast-like cells were positive for amelogenin, TrkA and CK14 but negative for p63, whereas odontoblast-like cells were negative for all antigens examined. In conclusion, a single intraperitoneal injection of MNU caused the development of odontomas in the molar region; these tumors were possibly derived from ERM.