Early cellular events in an actinomycin D-created dentin niche in the rat incisor

Administration of actinomycin D at a dose level of 0.375 microgram/g resulted in the selective disruption of developing odontoblasts at a critical stage of morphogenesis. A dentin niche was formed which was later repaired by cellular reparative dentin. The cellular changes which resulted in dentin niche formation were studied histologically and ultrastructurally in serial longitudinal and transverse sections from tissues obtained 10 h to 80 h following injection of the drug. Five stages were identified: initial destruction (10-20 h), rapid destruction (30-40 h), debris removal (50-60 h), proliferation (60-80 h) and matrix deposition (post 80 h). The cellular changes found in the dental papilla were considerably different from those found in inflammation, resolution and repair of fibrous connective tissue. These early stages were dominated by apoptosis and heterophagy, and after 80 h by disordered dentin matrix formation. The three-dimensional morphology of the defect was reconstructed from serial sections. The shape of the niche was the result of interference by actinomycin D in the patterns of proliferation and migration of the cells in the apical region of the rat incisor tooth.