Direct evidence of epithelial-mesenchymal interdependence in situ.

In the basal odontogenic zone of the mandibular incisor of the rat the cytological evidence of the toxicity of 40 mg cyclophosphamide per kg, 24 hours following a single intraperitoneal injection, was confined to the proliferating mesenchyme. Localised loss of precursors of odontoblasts cessation of basal odontogenesis and acellularity of the related part of the pulp ensured. The cells of the internal enamel epithelium bordering this region did not differentiate into ameloblasts and appeared atrophic. Upon recovery of the proliferating mesenchymal cell population odontogenesis was resumed basal to the zone of the cytotoxic injury. Pulpal connective tissue generating irregular dentine advanced from the reconstituted basal zone into the area of pulpal acellularity. This was followed by the differentiation of the peripheral stunted cells of the internal enamel epithelium into ameloblasts and locally delayed resumption of amelogenesis. These observations appear to offer direct evidence of epithelial-mesenchymal interdependence in situ.

Cytotoxicity of cyclophosphamide in the rat incisor.

Three of the 4 groups of 3 Wistar rats each were given 40 mg, 80 mg and 120 mg cyclophosphamide/kg respectively by single intraperitoneal injections. The fourth group was given 2 ml of normal saline as control. One animal from each group was killed after 1, 4 and 8 days. The incisor teeth of all experimental animals showed evidence of cytotoxic injury, which appeared to be more severe with increasing dosage, to the undifferentiated mesenchymal cells in the proliferating zone of the pulp close to the basal odontogenic epithelium, cessation of root growth and relative acellularity of the basal area of the pulp. Evidence of cytotoxicity to the odontogenic epithelium was seen only in the groups given 80 mg/kg and 120 mg/kg. Resolution of the cytotoxic injury and re-establishment of normal basal odontogenesis were seen in the 40 mg dose group by the eighth day but appeared to be slower with increasing dosage. It would seem that of the rapidly proliferating epithelial and mesenchymal odontogenic cells in the basal area of the rat incisor those in the mesenchyme may be most susceptible to the cytotoxicity of cyclophosphamide. The odontogenic epithelium may be resistant to the cytotoxicity of 40 mg cyclophosphamide/kg. The results may be of significance in the investigation of the mechanism of cytotoxicity of this cancer chemotherapeutic agent.