title: Effects of vincristine on the developing hamster tooth germ in vitro.
abstract: 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(-8)M-10(-4)M vincristine) on the developing tooth germ was the induction of mitotic arrests at the cervical loop and in the inter-cuspal regions. The 10(-4)M-10(-6)M vincristine doses were cytotoxic to most cells in the developing tooth germ. The 10(-7)M 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(-8)M 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(-7)M vincristine upwards. 10(-9)M vincristine, the lowest dose tested, did not induce any changes in the developing tooth germ. The organ culture data indicate that 10(-9)M vincristine is the highest (safe) dose which does not induce any toxic effects in the developing hamster tooth germ.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dept. Oral Cell Biol., ACTA, Amsterdam, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: Lyaruu
authors.forename: M A
authors.initials: MA
authors.lastname: van Duin
authors.forename: T J
authors.initials: TJ
authors.lastname: Bervoets
authors.forename: J H
authors.initials: JH
authors.lastname: Wöltgens
authors.forename: A L
authors.initials: AL
authors.lastname: Bronckers
mesh_terms: D000565:Ameloblasts / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004658:Enamel Organ / Q000187:drug effects / Q000473:pathology; D008938:Mitosis / Q000187:drug effects; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D010758:Phosphorus / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D014074:Tooth Calcification / Q000187:drug effects; D014083:Tooth Germ / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D002132:Calcium Radioisotopes; D010761:Phosphorus Radioisotopes; D010758:Phosphorus; D014750:Vincristine; D002118:Calcium