Effects of Vincristine on the Developing Hamster Tooth Germin Vitro

Vincristine is one of the cytostatic drugs present in cocktails commonly used for the treatment of cancer in children. The aim of this study was to evaluate biochemically and histologically the toxic effects of this drug on the developing tooth in vitro using the organ culture model in order to be able to predict what damage the drug can induce in the developing teeth from children undergoing anti-neoplastic chemotherapy.The most profound effect of the drug (10−8M-10−4M vincristine) on the developing tooth germ was the induction of mitotic arrests at the cervical loop and in the intercuspal regions. The 10−4M-10−6M vincristine doses were cytotoxic to most cells in the developing tooth germ. The 10−7M vincristine dose apart from induction of mitotic arrests, did not appear to be cytotoxic to the mature differentiated secretory cells. However, this dose induced incomplete nuclear polarization of the differentiating ameloblasts and odontoblasts. At 10−8M vincristine, the only effect observed were mitotic arrests; the secretory cells did not appear to have been affected at all. On the other hand, mineralization (TCA-soluble 45Ca and 32P uptake) was dose-dependently decreased from 10−7M vincristine upwards. 10−9M vincristine, the lowest dose tested, did not induce any changes in the developing tooth germ.The organ culture data indicate that 10−9M vincristine is the highest (safe) dose which does not induce any toxic effects in the developing hamster tooth germ. The 10 −8M vincristine dose inhibits cell proliferation (mitotic arrests) but does not affect the morphological integrity of the protein-secreting cells, i.e., secretory ameloblasts and odontoblasts or mineralization. Doses of ≥10−7M dose-dependently decrease mineralization while doses of ≥ 10−6M are highly cytotoxic and may even induce total destruction of the developing tooth germ. Thus using this model, it can be postulated that children given the usual therapeutic doses of this drug (∼ 4 × 10−6M vincristine peak serum concentration) during the early stages of tooth development will eventually exhibit serious defects in the erupted permanent dentition.