Karim A C, Bervoets T J, Lyaruu D M, Wöltgens J H, Bronckers A L
Department of Anatomy, University of Manitoba, Winnipeg, Canada.
Exp Toxicol Pathol. 1993 Feb;45(1):41-6. doi: 10.1016/S0940-2993(11)80453-7.
Second maxillary molars of 4-5 days old golden hamsters were exposed for 2 h in vitro to 1 mg/L adriamycin, rinsed and subsequently cultured up to 7 days without the drug. At days 3, 5 or 7 of culture the synthesis of extracellular tooth matrices and their mineralization were examined by measuring the incorporation of 3H-proline and the uptake of 45Ca and 32PO4 by the explants during a 24 h pulse labeling. Compared with unexposed control explants, exposure to adriamycin for the first 2 h of culture had no effect on total biosynthesis of proline-containing matrix proteins. However, at days 3 and 5 of culture it increased the quantity of water-soluble enamel matrix proteins (amelogenins). Adriamycin also strongly reduced the amount of organically-bound 32P-activity in a fraction extractable with guanidine-HC1-EDTA only, allegedly containing a mixture of mineral-associated proteins from both enamel and dentin. Since this decrease of 32P-activity coincided with the formation of osteodentin in the pulp as shown previously in histological and electron microscopical studies, it was speculated that osteodentin matrix may not contain the highly phosphorylated, dentin-specific phosphoproteins (DPP). Adriamycin also affected the uptake of 45Ca and 32PO4. At day 3 these values were slightly higher than control values but lower at days 5 and 7. It therefore appears that a 2 h exposure to adriamycin in concentrations as low as 1 mg/L causes an acceleration of secretory amelogenesis by tooth germs in vitro. It also induces pulp cells to form osteodentin.
将4 - 5日龄金黄地鼠的上颌第二磨牙在体外暴露于1毫克/升阿霉素中2小时,冲洗后在无药物的情况下培养7天。在培养的第3、5或7天,通过测量外植体在24小时脉冲标记期间3H - 脯氨酸的掺入以及45Ca和32PO4的摄取,来检测细胞外牙基质的合成及其矿化情况。与未暴露的对照外植体相比,在培养的最初2小时暴露于阿霉素对含脯氨酸的基质蛋白的总生物合成没有影响。然而,在培养的第3天和第5天,它增加了水溶性釉质基质蛋白(釉原蛋白)的量。阿霉素还强烈降低了仅能用盐酸胍 - 乙二胺四乙酸提取的部分中有机结合的32P活性,据称该部分含有来自釉质和牙本质的与矿物质相关的蛋白质混合物。由于如先前组织学和电子显微镜研究所示,这种32P活性的降低与牙髓中骨样牙本质的形成同时发生,因此推测骨样牙本质基质可能不包含高度磷酸化的牙本质特异性磷蛋白(DPP)。阿霉素还影响了45Ca和32PO4的摄取。在第3天,这些值略高于对照值,但在第5天和第7天较低。因此,似乎在体外,低至1毫克/升浓度的阿霉素暴露2小时会导致牙胚分泌性釉质形成加速。它还诱导牙髓细胞形成骨样牙本质。