Fate of fluoride-induced subameloblastic cysts in developing hamster molar tooth germs.

White opacities and pits are developmental defects in enamel caused by high intake of fluoride (F) during amelogenesis. We tested the hypothesis that these enamel pits develop at locations where F induces the formation of sub-ameloblastic cysts. We followed the fate of these cysts during molar development over time. Mandibles from hamster pups injected with 20mg NaF/kg at postnatal day 4 were excised from 1h after injection till shortly after tooth eruption, 8 days later. Tissues were histologically processed and cysts located and measured. Cysts were formed at early secretory stage and transitional stage of amelogenesis and detected as early 1h after injection. The number of cysts increased from 1 to almost 4 per molar during the first 16h post-injection. The size of the cysts was about the same, i.e., 0.46±0.29×10(6)µm(3) at 2h and 0.50±0.35×10(7)µm(3) at 16h post-injection. By detachment of the ameloblasts the forming enamel surface below the cyst was cell-free for the first 16h post-injection. With time new ameloblasts repopulated and covered the enamel surface in the cystic area. Three days after injection all cysts had disappeared and the integrity of the ameloblastic layer restored. After eruption, white opaque areas with intact enamel surface were found occlusally at similar anatomical locations as late secretory stage cysts were seen pre-eruptively. We conclude that at this moderate F dose, the opaque sub-surface defects with intact surface enamel (white spots) are the consequence of the fluoride-induced cystic lesions formed earlier under the late secretory-transitional stage ameloblasts.

Ultrastructure of altered rat enamel beneath fluoride-induced cysts.

The effect of a single injection of sodium fluoride (60 mg/kg) on the development of rat molar enamel beneath fluoride-induced subameloblastic cysts was studied by transmission electron microscopy using undecalcified sections. Three bands of altered enamel were identified and defined as the cyst surface band, the hypoplastic band, and the hypercalcified band. The irregular cyst surface band, not previously described, was found to have two components: electron-dense enamel globules and organic spherules. The electron-dense globules consisted of small, randomly arranged crystals (confirmed by selected area electron diffraction) occurring within a stippled organic matrix. The organic spherules have staining properties similar to stippled material and lack a crystalline component. They may be a form of organic material being extruded from the underlying developing enamel. The critical role of normal matrix production and ameloblast Tomes' process structure on the development of the crystal orientation and rod pattern is discussed.

Ultrastructure of fluoride-induced cysts in the rat molar enamel organ.

Earlier studies have shown that a single high dose of fluoride induces subameloblastic cysts separated by morphologically unaltered ameloblasts in the developing rat molar. In the present investigation, the ultrastructure of both the ameloblasts forming the cystic wall, and the cells within the cystic lumina were studied by means of transmission electron microscopy. It was shown that 24 h after fluoride injection the ameloblasts of the cystic wall showed various degrees of cytoplasmic and nuclear alterations. Some cells displayed signs of necrosis as indicated by condensation of the chromatin. The cytoplasmic changes varied from altered organelle morphology to fragmentation and almost complete shedding of the whole cytoplasm. In the ameloblasts of the cystic wall secretory products accumulated intracellularly, in distended rough endoplasmatic reticulum, in vesicles of the Golgi region and extracellularly between ameloblasts as well as between cells in the stratum intermedium, indicating an altered matrix secretion. Electron lucent material, cell and cell fragments were found in the cystic lumina, the two latter apparently originating from the ameloblastic layer. The degenerative changes seemed to follow the normal pattern of cell degeneration.

Scanning electron microscopy of fluoride-induced disturbances on the enamel surface of rat molars.

Rats were given a single high dose of fluoride at the age of 5 days and killed after 24 h, 10 or 15 days. The maxillary first molars were prepared for scanning electron microscopic examination. It was concluded that a single dose of fluoride, preferentially affecting ameloblasts with a high secretory activity, leads to the formation of subameloblastic cysts and enamel hypoplasias covered with granular deposits.

Fluoride-induced cystic changes in the enamel organ of the rat molar.

Many substances have been found to cause enamel disturbances in toxic doses, and it has been postulated that these disturbances are linked to the formation of sub-ameloblastic cysts. In the present investigation, fluoride-induced sub-ameloblastic cysts in developing rat molars were related to fluoride dose, age of the animals, and the plasma fluoride level. The sub-ameloblastic cysts, which developed predominantly towards the end of the secretory stage of amelogenesis, appeared shortly after fluoride administration and regressed within 3 days. Hypoplasias and internal defects were found in the enamel under the disturbed ameloblast layer. The highest plasma fluoride levels were found in the youngest animals 24 h after injection. The frequency and size of the sub-ameloblastic cysts were clearly related to the fluoride-dose and age of the animal and, subsequently, to the plasma fluoride level.

Experimental odontogenic cysts induced by in vitro 4-nitroquinoline 1-oxide (4NQO) treatment of F344 rat incisor tooth germs.

This study was designed to establish an experimental animal model for elucidating the early stages of odontogenic cysts and tumors. It involves the in vitro treatment of tooth germs with 4-nitroquinoline 1-oxide (4NQO) at the early bell stage and their subsequent transplantation into the kidney subcapsular space. While all tooth germ transplants of the control group not exposed to the carcinogen showed continued tooth development with no pathological lesions, 21 of 23 4NQO-treated tooth germs developed into similar appearing keratinized cysts with or without associated tooth structures. The remaining two transplants failed to develop cysts and formed only a tooth. The present experimental procedure was effective in inducing keratinized cystic lesions that exhibit some similarities to human odontogenic keratocysts or primordial cysts.

Gingival eruption cysts induced by cyclosporine administration to neonatal dogs.

OBJECTIVES: The purpose of this paper is to report the development of extensive, gingival eruption cyst formation in neonatal dogs during chronic administration of cyclosporine, which regressed after treatment ceased. MATERIALS AND METHODS: As part of an investigation of the efficacy of adenoviral-mediated gene therapy in a canine model of Duchenne Muscular Dystrophy (DMD), 26 Golden retriever pups were given intramuscular injections of adenoviral gene constructs (at 2-5 days old) either with (15 pups) or without (9 pups) concomitant immunosuppression using oral cyclosporine (from 1 to 3 days old). RESULTS: The daily administration of cyclosporine to Golden Retriever pups from 1 to 3 days of age resulted in the formation of eruption cysts over the incisors after approximately 3 weeks of treatment. The gingiva over the remaining teeth became swollen. However unlike the incisors, part of the crown erupted through the gingiva. Continuous treatment for 60-90 days was associated with persistence and expansion of the cysts over the incisor teeth. The cysts resolved within 1 month if cyclosporine administration was discontinued. Movement of incisors within the jaws was not appreciably affected when compared with age-matched controls. CONCLUSION: Chronic cyclosporine administration to neonatal dogs induces the formation of eruption cysts over the incisors, which is reversible once treatment is discontinued and does not affect intraosseous eruption.