Lyaruu D M, van Duin M A, Bervoets T J, Bronckers A L, Wöltgens J H
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands.
Cancer Detect Prev. 1999;23(4):343-50. doi: 10.1046/j.1525-1500.1999.99028.x.
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 ([3H]thymidine uptake), and insoluble [32P] phosphate uptake (phosphorylation of macromolecules). [45Ca]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 mainly associated with those regions that were in the proliferating stage at the onset of anticancer chemotherapy.
本研究的目的是在器官培养条件下评估柔红霉素对牙齿发育的细胞毒性作用。将3日龄仓鼠上颌第二磨牙在体外暴露于10^-8 - 10^-4 M的柔红霉素中24小时，然后进行生化和组织学评估。在10^-6 M时，柔红霉素剂量依赖性地降低了牙胚干重、细胞增殖（[3H]胸腺嘧啶核苷摄取）以及不溶性[32P]磷酸盐摄取（大分子磷酸化）。作为矿化标志物的[45Ca]钙摄取仅在测试的最高浓度（10^-4 M）下受到显著影响。组织学上，10^-6 M的柔红霉素诱导增殖细胞而非分化的蛋白质分泌细胞发生坏死。然而，在10^-4 M时，所有细胞均死亡。这些结果表明柔红霉素对牙胚的增殖细胞具有特别的毒性。因此，可以推测接受柔红霉素治疗的儿童恒牙可能出现缺陷，主要与抗癌化疗开始时处于增殖阶段的那些区域有关。
