Hexachlorobenzene-Induced Incisor Degeneration in Sprague—Dawley Rats

Abstract

Hexachlorobenzene (HCB) was administered to female Sprague-Dawley rats in a 13-week toxicity study conducted for the National Toxicology Program (NTP). Groups of 10 rats were treated by gavage with 0.0, 0.03, 0.1, 0.3, 1.0, 3.0, 10, or 25 mg/kg HCB in corn oil 5 days/week for 13 weeks. Dose-dependent, region-specific, maxillary incisor degeneration was observed in animals given HCB at doses of 1.0 mg/kg/day and higher. Treatment with 1.0 mg/kg/day resulted in focal mesenchymal cell vacuolation and focal osteodentin formation within the pulp. Lesions were restricted to a short linear region subjacent to the odontoblast layer along the lateral aspect of the incisor at the level of the dentin-enamel interface. When observed in both incisors, lesions were bilaterally symmetric. Treatment with 3.0 mg/kg/day resulted in lateral and medial pulp lesions and focal odontoblast degeneration with dentin niche formation along the lateral incisor margin in some animals. Treatment with 10 mg/kg/day resulted in a higher incidence of lateral dentin niches and a low incidence of medial dentin niches. In animals treated with 25 mg/kg/day, a high incidence of bilaterally symmetric, lateral and medial, dentin niches were observed. The morphology and distribution of HCB-induced incisor lesions in rats are consistent with injury to a selective population of preodontoblasts.

Involvement of the Klotho Protein in Dentin Formation and Mineralization

“…It is interesting that the histological abnormality in the klotho −/− incisor is restricted to its labial region. A similar change in the klotho −/− mice has been reported in the rat incisor suffering from HHM (hypercalcemia of malignancy; Kato et al, 2003) or treated with hexachlorobenzen (Long et al, 2004). On the other hand, Savage et al (2006) reported dentin malformations restricted to the lingual side in the mandibular incisor of p20C/EBPbeta transgenic mice.…”

Immunohistochemical Detection of PTHrP and PTH/PTHrP Receptor 1 on the Odontoblastic Reparative Process after Actinomycin D Treatment in Rats

“…On day 7, the lesions moved further toward the columnar odontoblastic area, and formed fully bloomed dentin niche with the histopathological character of sharply demarcated recessed areas of dentin as defined in previous reports [12][13][14][15][16][17][18][19] . Based on this morphological sequence from the onset of cell damage to dentin niche formation and the fact that many different types of cytotoxic agents with different modes of action can consistently induce dentin niche, the lesion is considered to be the repair response of odontoblasts to cell damage [12][13][14][15][16][17][18][19] . In addition, previous autoradiographic investigations have shown that cuboidal odontoblastic cells are derived from surviving odontoblasts and hypertrophic pulpal cells, and they are considered to be a signature of regeneration of the odontoblastic layer 14,19 .…”

“…Interestingly, one of the odontoblastic lesions observed in this model was identical to dentin niche, which is known to consistently develop after administration of a number of cytotoxic agents with different modes of action. Dentin niche is considered to be an odontoblastic repair response to cell damage, because of the consistency and the outcomes of time course observations of its development [12][13][14][15][16][17][18][19] . PTHrP and/or PTHR1 are known to be expressed in emerging cells during the repair processes in bone, cartilage, and skin [20][21][22][23][24] , as well as in cells contributing to normal dentinogenesis [25][26][27] .…”

Incisor Degeneration in Rats Induced by Vascular Endothelial Growth Factor/Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibition

“…Also in healthy mice, VEGF signaling inhibition resulted in a reduction in the number of tracheal mucosal (Karim 1990;Satoh et al 2001) Colchicine Ameloblast degeneration, inhibition of enamel-matrix secretion (Nishikawa 2002) Dioxin Low columnar to cuboidal odontoblasts, odontoblast cell death; arrest of dentin formation; squamous metaplasia and proliferation of the enamel organ with apoptosis; pulp cell death; defects of dentin and enamel mineralization (Alaluusua and Lukinmaa 2006;Kiukkonen et al 2002) 5-Fluorouracil Disorganization of odontoblasts, focal dentin defects (Satoh et al 2001). Hexachlorobenzene Odontoblast degeneration, dentin recesses, irregular dentin matrix organization and cellular inclusions; pulp mesenchymal cell formation, osteodentin formation within the pulp (Long, Herbert, and Nyska 2004).…”