Published in Cancer Detection and Prevention 1999; 23(4):343-350.

Daunorubicin-Induced Pathology in the Developing Hamster Molar Tooth Germ in Vitro

D. M. Lyaruu, Ph.D., M. A. van Duin, B.Sc., T. J. M. Bervoets, B.Sc., A. L. J. J. Bronckers, Ph.D., and J. H. M. Wöltgens, Ph.D., D.D.S.

Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands.

Address all correspondence and reprint requests to: D. M. Lyaruu, Tooth Dev. Sect., Department of Oral Cell Biol., ACTA, Vrije Universiteit, v.d. Boechorststraat. 7, 1081 BT Amsterdam, The Netherlands.

ABSTRACT. The aim of this study was to evaluate, under organ culture conditions, the cytotoxic effects of daunorubicin on tooth development. Three-day-old maxillary hamster second molars were exposed for 24 h in vitro to 108 - 10-4 M daunorubicin and then evaluated biochemically and histologically. At (10-6 M daunorubicin dose-dependently decreased tooth germ dry weight, cell proliferation ([3 H]thymidine uptake), and insoluble [32 P]phosphate uptake (phosphorylation of macromolecules). [45 Ca]calcium uptake, a marker for mineralization, was significantly affected only at the highest concentration (10-4 M) tested. Histologically, 10-6 M daunorubicin induced necrosis of the proliferating but not the differentiated protein-secreting cells. At 10-4 M, however, all cells were dead. These results indicate that daunorubicin is particularly toxic to the proliferating cells of the tooth germ. Thus, it can be postulated that children treated with daunorubicin may develop defects in the erupted teeth malnly associated with those regions that were in the proliferating stage at the onset of anticancer chemotherapy.

KEY WORDS: anticancer chemotherapy, cell proliferation, chemoprevention, hamster, organ culture, tooth development.