Summary
Cyclophosphamide-induced changes in rodent odontogenesis were investigated by light and electron microscopy in four-day-old Sprague Dawley rats given one injection of 40 mg/kg of body weight of cyclophosphamide and killed at intervals of one hour, one day, one week and two weeks. Incisor and molar teeth were dissected from the animals, fixed in 2.0% glutaraldehyde in 0.1 M sodium cacodylate with 3.4% sucrose, and subsequently some were incubated for alkaline phosphatase reaction, and embedded in Spurr's medium for sectioning at light- and electron-microscopic levels. From three days a cell-sparse zone was created in the pulp in the growing end of the tooth and progressive cellular changes were observed which became more severe in the one-week and two-week specimens. Subodontoblast and adjacent pulpal cells were the most affected showing nuclear changes, damage to, or loss of, organelles, and inclusion bodies. Odontogenic epithelium was less affected and odontoblasts appeared to be unaffected by the drug. A new irregular matrix was laid down in the defect area and seemed to be the product of depolarized odontoblasts. This new matrix showed alkaline phosphatase activity, as did the cells embedded in it, and later it became mineralized. It is speculated that the polarity of odontoblasts might be maintained by an intact subodontoblastic layer; when this is lost the odontoblasts become depolarized and capable of secreting matrix from both ends.
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References
Adatia AK (1975a) The effects of cyclophosphamide on odontogenesis in the rat. Archs Oral Biol 20:141–144
Adatia AK (1975b) Cytotoxity of cyclophosphamide in the rat incisor. Br J Cancer 32:208–218
Adatia AK (1980) Direct evidence of epithelial-mesenchymal interdependence in situ. J Anat 130:469–478
Adkins KF (1967) The effect of 1200 R of X-radiation on dentinogenesis in the mandibular teeth of rats. Archs Oral Biol 12:1569–1576
Brooker P (1964) Reaction of alkylating agents with nuclei acids. In: Platner PA (ed) Proc Int Symp Chemother Cancer Lugano, Elsevier, Amsterdam, p 32–43
Calabresi P, Parks RE (1970) Alkylating agents, antimetabolites, hormones and other antiproli-ferative agents. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics 4th ed McMillan, New York, Chap 62, p 1348–1395
Eichenberry EF, Brodsky B, Parry DAD (1982a) Collagen fibril morphology in developing chick metatarsal tendons: 1. X-ray diffraction studies. Int J Biol Macrobiol 4:322–329
Eichenberry EF, Brodsky BB, Craig AS, Parry DAD (1982b) Collagen fibril morphology in developing chick metatarsal tendon. 2. Electron microscope studies. Int J Biol Macromol 4:393–398
Koppang HS (1973a) Histomorphologic investigations on the effect of cyclophosphamide on dentinogenesis of the rat incisor. Scand J Dent Res 81:383–396
Koppang HS (1973b) Autoradiographic investigations on the effect of cyclophosphamide on dentinogenesis of the rat incisor. Scand J Dent Res 81:397–405
Mayahara H, Hirano H, Saito T, Ogawa K (1967) The new lead citrate method for the ultracytochemical demonstration of activity of non-specific alkaline phosphatase (orthophosphoric monoester phosphohydrolase). Histochemie 11:88–96
Norlinder H (1971) Malformations in newborn rats treated with a single dose of cyclophosphamide. Acta Soc Med Upsal 76:87–90
Price CC (1958) Fundamental mechanisms of alkylation. Am NY Acad Sci 68:663–338
Reade PC, Roberts ML (1978) Some long term effects of cyclophosphamide on the growth of rat incisor teeth. Archs Oral Biol 23:1001–1005
Ross WCJ (1962) Biological alkylating agents. Butterworth, London
Vahlsing HL, Feringer ER, Britten AG, Kinning WK (1975) Dental abnormalities in rats after a single dose of cyclophosphamide. Cancer Res 35:2190–2202
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Orams, H.J. Cyclophosphamide-induced changes in rodent odontogenesis. Cell Tissue Res. 234, 679–689 (1983). https://doi.org/10.1007/BF00218659
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DOI: https://doi.org/10.1007/BF00218659