Lyaruu D M, van Duin M A, Bervoets T J, Wöltgens J H, Bronckers A L
Dept. Oral Cell Biol., ACTA-Vrije Universiteit, Amsterdam, The Netherlands.
Eur J Oral Sci. 1997 Feb;105(1):52-8. doi: 10.1111/j.1600-0722.1997.tb00180.x.
The aim of this study was to evaluate the toxic effects of actinomycin D on the developing hamster tooth germ in organ culture. Hamster tooth 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-dependently (> or = 10(-7) M) decreased the tooth germ dry weight but mineralization was affected only by doses > or = 10(-5) M. However, the uptakes of TCA-insoluble 32P and [3H]thymidine were significantly reduced dose-dependently from > or = 10(-8) M actinomycin D, indicating that the drug inhibits 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 proliferating pre-odontoblasts followed by pre-ameloblasts; the mature secretory ameloblasts and odontoblasts appeared unaffected. Higher doses resulted in increased cytotoxicity to the secretory cells and, eventually, total 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 toxicity of the drug to the tooth organ.
本研究的目的是评估放线菌素D对器官培养中正在发育的仓鼠牙胚的毒性作用。在分泌性釉质形成早期的仓鼠牙胚在体外暴露于10(-9)M - 5×10(-5)M的放线菌素D中24小时。放线菌素D剂量依赖性地（≥10(-7)M）降低牙胚干重，但仅≥10(-5)M的剂量会影响矿化。然而，从≥10(-8)M放线菌素D开始，三氯乙酸不溶性32P和[3H]胸苷的摄取量呈剂量依赖性显著降低，表明该药物抑制含磷酸盐大分子的合成以及DNA合成。组织学上，10(-8)M放线菌素D是对正在发育的牙胚中任何细胞类型均无毒性的最低剂量。在10(-7)M放线菌素D时，最敏感的细胞是增殖的前成牙本质细胞，其次是前成釉细胞；成熟的分泌性成釉细胞和成牙本质细胞似乎未受影响。更高的剂量导致对分泌细胞的细胞毒性增加，最终大多数细胞完全退化。数据表明，在牙齿发育期间使用含放线菌素D（血清水平>10(-7)M）的抗癌化疗鸡尾酒治疗的儿童，可能由于药物对牙齿器官的毒性而在成熟牙列后期出现缺陷。
