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Anomalous Growth of Rat Incisor Teeth during Chronic Intermittent Vitamin A Deficiency

Differentiation Control Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892 ^* Microbiological Associates, Inc., Bethesda, MD 20816

Rapid, synchronous and repeating cycles of marginal retinoic acid sufficiency and deficiency were produced in rats by following an established protocol. During cycles 11–15 (343–464 days after weaning), 17 of 24 rats (71%) developed tumor-like masses in the connective tissue surrounding the formative ends of one or both upper incisor teeth. The masses were composed of cords of odontogenic epithelium surrounded by a mantle of mesenchyme. Lakes of predentine, associated with foci of keratinized epithelium, were randomly distributed. On the basis of current understanding of odontogenesis, we propose that periodically disturbed differentiation of pulpal mesenchymal cells to dentin-secreting odontoblasts was pivotal to development of the masses. During deficiency, dentin secretion is impaired, the dentine wall perforates and with time the odontogenic epithelium and pulp herniate into the surrounding connective tissues. We propose that the incisal masses arose because the pulpal mesenchyme continued to grow and its secretion product, dentine, continued to be deposited (during periods of vitamin A sufficiency) in an ectopic site where functional attrition from mastication could not occur.

KEY WORDS: • vitamin A deficiency • odontogenesis • retinoic acid • odontoblasts

¹ Permanent address: Department of Pathology, University of Maryland, School of Medicine, 10 South Pine Street, Baltimore, MD 21201.

² Address for reprints: Luigi M. De Luca, Building 37, Room 3A17, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Manuscript received 10 October 1986. Revision accepted 3 March 1987.