EFFECTS OF ACTINOMYCIN-D ON DEVELOPING HAMSTER MOLAR TOOTH GERMS IN-VITRO

The aim of this study was to evaluate the toxic effects of actinomycin D on the developing hamster tooth germ in organ culture. Hamster toot h germs during early secretory amelogenesis were exposed in vitro for 24 h to 10(-9) M-5 x 10(-5) M actinomycin D. Actinomycin D dose-depend ently (greater than or equal to 10(-7) M) decreased the tooth germ dry weight but mineralization was affected only by doses greater than or equal to 10(-5) M. However, the uptakes of TCA-insoluble P-32 and [H-3 ]thymidine were significantly reduced dose-dependently from greater th an or equal to 10(-8) M actinomycin D, indicating that the drug inhibi ts the synthesis of phosphate-containing macromolecules as well as DNA synthesis. Histologically, 10(-8) M actinomycin D was the lowest dose which was not toxic to any cell type in the developing tooth germ. At 10(-7) M actinomycin D, the most sensitive cells were the proliferati ng pre-odontoblasts followed by pre-ameloblasts; the mature secretory ameloblasts and odontoblasts appeared unaffected. Higher doses resulte d in increased cytotoxicity to the secretory cells and, eventually, to tal degeneration of most cells. The data suggest that children treated for cancer during tooth development using anti-chemotherapy cocktails containing actinomycin D (serum levels >10(-7) M) may develop defects later on in the mature dentition as a direct consequence of the toxic ity of the drug to the tooth organ.