[Ultrastructural changes in rat-incisor dentinogenic cells after administration of 5-fluorouracil]

Single intraperitoneal injections (180 mg/kg) of 5-fluorouracil (5-FU) were administered to male Wistar rats weighing 100 g each. After 1, 2, 3, 4, 5, 7, 10 and 21 days, the animals were fixed by perfusion with a mixture of 2.5% glutaraldehyde and 2.0% paraformaldehyde. The maxillary incisors were dissected out; and optical-microscopy, microradiography, and transmission electron-microscopy were made of changes occurring in the dental-papilla cells, odontoblasts, and dentin matrix. 1. One day after the 5-FU injection, considerable amount of damage had occurred in the basal portion of the incisor forming a large void in the dental-papilla (cell-free region) immediately below the inner enamel epithelium. But, 4 days after the injection, the cell-free region was filled again with numerous newly regenerated dental-papilla cells (reparative region). Thereafter these cells differentiated as regular odontoblasts. 2. In 1 day after the injection, dental-papilla cells that had begun differentiating into odontoblasts degenerated and atrophied (degeneration region). Round cells appeared on the pulp sides of degenerated and atrophied odontoblasts 3 days after the injection. These cells increased in both size and number and formed a hard tissue in which the degenerated odontoblasts had embedded. The matrix of the newly forming hard tissue was composed of closely arranged collagen fibrils. Matrix vesicles were observed in the initial stage of its mineralization. Dentin had deposited on the pulp side of this hard tissue 21 days after the injection. 3. Dentin formation in the reparative region began 7 days after the injection; and, by the twenty-first day, ordinary dentin thickness had been attained. In the degeneration region, however, a little dentin was formed. In contrast, on both sides of the degeneration region, dentin formed in a virtually normal fashion and grew thicker with the passing of time, creating a deep, bowl-shaped concavity in the degeneration region.