Daunorubicin-induced pathology in the developing hamster molar tooth germ in vitro

The aim of this study was to evaluate, under organ culture conditions, the cytotoxic effects of daunorubicin on tooth development. Three-day-old maxil lary hamster second molars were exposed for 24 h in vitro to 10(8)-10(-4) M daunorubicin and then evaluated biochemically and histologically. At 10(-6 ) M daunorubicin dose-dependently decreased tooth germ dry weight, cell pro liferation ([H-3]thymidine uptake), and insoluble [P-32]phosphate uptake (p hosphorylation of macromolecules). [Ca-45]calcium uptake, a marker for mine ralization, was significantly affected only at the highest concentration (1 0(-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 daunorubi cin is particularly toxic to the proliferating cells of the tooth germ. Thu s, it can be postulated that children treated with daunorubicin may develop defects in the erupted teeth mainly associated with those regions that wer e in the proliferating stage at the onset of anticancer chemotherapy.