Effects of actinomycin D on developing hamster molar tooth germs in vitro.

The aim of this study was to evaluate the toxic effects of actinomycin D on the developing hamster tooth germ in organ culture. Hamster tooth germs during early secretory amelogenesis were exposed in vitro for 24 h to 10(-9) M-5 x 10(-5) M actinomycin D. Actinomycin D dose-dependently (> or = 10(-7) M) decreased the tooth germ dry weight but mineralization was affected only by doses > or = 10(-5) M. However, the uptakes of TCA-insoluble 32P and [3H]thymidine were significantly reduced dose-dependently from > or = 10(-8) M actinomycin D, indicating that the drug inhibits the synthesis of phosphate-containing macromolecules as well as DNA synthesis. Histologically, 10(-8) M actinomycin D was the lowest dose which was not toxic to any cell type in the developing tooth germ. At 10(-7) M actinomycin D, the most sensitive cells were the proliferating pre-odontoblasts followed by pre-ameloblasts; the mature secretory ameloblasts and odontoblasts appeared unaffected. Higher doses resulted in increased cytotoxicity to the secretory cells and, eventually, total degeneration of most cells. The data suggest that children treated for cancer during tooth development using anti-chemotherapy cocktails containing actinomycin D (serum levels > 10(-7) M) may develop defects later on in the mature dentition as a direct consequence of the toxicity of the drug to the tooth organ.

Fluoride content of infant formulae in Australia.

The prevalence of dental fluorosis in Australia and the United States of America has increased in both optimally fluoridated and non-fluoridated areas. This has been attributed to an increase in the fluoride level of food and beverages through processing with fluoridated water, inadvertent ingestion of fluoride toothpaste, and the inappropriate use of dietary supplements. A major source of fluoride in infancy is considered to be infant formula which has been implicated as a risk factor for fluorosis in a number of studies. In this study the fluoride content of the infant formulae commonly used in Australia was determined. The acid diffusible fluoride of each powdered formula was isolated by microdiffusion and measured using a fluoride ion-specific electrode. The fluoride content of milk-based formulae ranged from 0.23 to 3.71 micrograms F/g and for soy-based formulae from 1.08 to 2.86 micrograms F/g. When reconstituted, according to the manufacturer's directions, with water not containing fluoride, the formulae ranged in fluoride content from 0.031 to 0.532 ppm, with the average fluoride content 0.240 ppm. Using average infant body masses and suggested volumes of formula consumption for infants 1-12 months of age, possible fluoride ingestion per kg body mass was estimated. None of the formulae, if reconstituted using water containing up to 0.1 ppm F, should provide a daily fluoride intake above the suggested threshold for fluorosis of 0.1 mg F/kg body mass. However, if reconstituted with water containing 1.0 ppm F they should all provide a daily fluoride intake of above the suggested threshold for fluorosis with intakes up to 2-3 times the recommended upper 'optimal' limit of 0.07 mg/kg body mass. Under these conditions the water used to reconstitute the formulae would provide 65-97 percent of the fluoride ingested. These figures are likely to be overestimates due to the intake of nutrients from other sources reducing formulae consumption and also due to the lower bioavailability of fluoride from milk-based formulae. Further, it is generally believed that the maturation stage of enamel formation is the critical period for fluorosis development by chronic, above-threshold fluoride exposure. The maturation stage for the anterior permanent teeth, however, is after the first twelve months of life where fluoride intake from infant formula consumption per kg body mass is highest. The level of fluoride in the commonly used Australian formulae would suggest that infant formula consumption alone is unlikely to be a risk factor for dental fluorosis in a non-fluoridated community, but could make a major contribution to an infant's daily fluoride intake. However, prolonged consumption (beyond 12 months of age) of infant formula reconstituted with optimally-fluoridated water could result in excessive amounts of fluoride being ingested during enamel development of the anterior permanent teeth and therefore may be a risk factor for fluorosis of these teeth.

Changes in the plasma electrolytes and metabolites of the rat following acute exposure to sodium fluoride and strontium chloride.

Acute exposure of rats to strontium or fluoride by i.p. injection of sodium fluoride or strontium chloride resulted in a systemic response in which changes occurred in the plasma electrolytes and metabolites. Strontium resulted in a rapid but temporary hypercalcaemia while fluoride produced a temporary hypocalcaemia. There was no significant hypophosphataemia after fluoride and only a transient hypophosphataemia with strontium. There was some indication of kidney damage and a general stress response following fluoride injection. These results do not support the hypothesis that interglobular dentine is associated with hypophosphataemia or hypoplastic enamel with hypocalcaemia and are in conflict with the observation that the formation of interglobular dentine following the injection of lead acetate is associated with hyperphosphataemia and hypercalcaemia.

The effect of a single dose of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) on presecretory ameloblast differentiation in rat incisors.

A single, high dose of HEBP to rats results in a triad of lesions along the mineralizing front of the incisor enamel. One type of lesion is a shallow groove crossing the apical enamel surface. The purpose of this study was to explore the pathogenesis of this "demarcation groove", and to characterize changes in the involved regions of amelogenesis. Rats were given a subcutaneous dose of 10 mg/kg body weight of HEBP and sacrificed by vascular perfusion at intervals ranging from 1 to 36 hours. Mandibular incisors were processed for light and electron microscopy. The region of ameloblasts facing dentin was divided into two subregions: A region of ameloblasts facing unmineralized dentin, comprising a posterior (Aud/p) and an anterior portion (Aud/a), and a region of ameloblasts facing mineralized dentin (Amd). The progressive apical mineralization of the predentin was arrested up to 12 hours after injection of HEBP, while ameloblasts related to already mineralizing dentin continued to differentiate and secrete enamel matrix. At 8 hours the dentin and enamel layers had assumed a common apical border at the start of Amd, marking the position of the future demarcation groove. The length of Aud/p remained constant, Aud/a doubled in length, and Amd was drastically reduced up to 24 hours after injection of HEBP. The normal migration rate of the ameloblasts was unaffected by HEBP. Accumulations of ameloblast secretory products occurred at certain time intervals between the cell apices, but no morphological changes were recorded in the organelles. Most of the changes observed may be indirect in nature resulting from the physico-chemical effect of HEBP on normal mineralization of dentin and enamel. However, further studies are needed to elucidate possible direct cellular effects on ameloblasts.