Shih S D, Rees T D, Miller E G, Wright J M, Iacopino A M
Department of Periodontology, Harvard School of Dental Medicine, Boston, MA, USA.
J Periodontol. 1996 Nov;67(11):1224-32. doi: 10.1902/jop.1996.67.11.1224.
Growth factors are multi-functional and multi-targeted proteins which play a significant role in wound healing. Platelet-derived growth factor B-chain homodimer (PDGF-BB) and insulin-like growth factor-1 (IGF-1) have demonstrated efficacy for periodontal regeneration in animal models. Although primarily associated with wound healing, PDGF-BB and IGF-1 also facilitate growth of a number of malignant neoplasms. Of particular concern to periodontists is epithelial dysplasia, a necessary precursor to squamous cell carcinoma, the most common oral malignancy. Certain risk factors for oral cancer, such as tobacco, age, and alcohol, are also associated with an increased incidence of periodontal disease. The effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia have not previously been reported. The purpose of this study was to examine the effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia induced in the buccal cheek pouch of the Syrian golden hamster. A total of 66 hamsters received 18 applications of 0.5% dimethylbenzanthracene (DMBA), a topical carcinogen, over a 6-week period for the induction of dysplasia. The hamsters were subsequently divided into a baseline and 3 experimental groups (growth factors, saline vehicle, untreated control). Following the final DMBA application (day 0), the baseline group (N = 6) was sacrificed, the growth factor group (N = 21) received a single injection in the cheek pouch containing 4 micrograms of PDGF-BB and 4 micrograms of IGF-1 in saline, the saline group (N = 19) received an injection in the cheek pouch containing the saline vehicle only, and the untreated control group (N = 20) received no injection. Animals in experimental groups were sacrificed on days 3, 6, and 10. The cheek pouches were harvested for histologic and histochemical evaluation. Dysplasia was histologically graded from 0 to 4. Statistical analysis of the histologic data revealed no significant differences either by sacrifice date or by group. Histochemical evaluation, via staining for gamma-glutamyl transpeptidase (GGT), a marker for dysplastic cell colonies, revealed that the density of GGT-positive cells in experimental groups differed significantly from baseline levels. No significant differences were detected between experimental groups. There was poor correlation between the density of GGT-positive cells and the histologic grading of dysplasia. It is concluded that exposure to PDGF-BB and IGF-1 had no demonstrable effect on epithelial dysplasia in this hamster model.
生长因子是多功能、多靶点的蛋白质，在伤口愈合中发挥着重要作用。血小板衍生生长因子B链同二聚体（PDGF-BB）和胰岛素样生长因子-1（IGF-1）已在动物模型中显示出对牙周再生的疗效。虽然PDGF-BB和IGF-1主要与伤口愈合相关，但它们也促进多种恶性肿瘤的生长。牙周病医生特别关注的是上皮发育异常，它是鳞状细胞癌（最常见的口腔恶性肿瘤）的必要前驱病变。口腔癌的某些危险因素，如烟草、年龄和酒精，也与牙周病发病率的增加有关。此前尚未报道过PDGF-BB和IGF-1联合使用对上皮发育异常的影响。本研究的目的是研究PDGF-BB和IGF-1联合使用对叙利亚金黄地鼠颊囊诱导的上皮发育异常的影响。总共66只地鼠在6周内接受了18次0.5%二甲基苯并蒽（DMBA，一种局部致癌物）涂抹以诱导发育异常。随后，地鼠被分为一个基线组和3个实验组（生长因子组、生理盐水组、未处理对照组）。在最后一次涂抹DMBA（第0天）后，处死基线组（N = 6），生长因子组（N = 21）在颊囊内注射一次含有4微克PDGF-BB和4微克IGF-1的生理盐水，生理盐水组（N = 19）在颊囊内仅注射生理盐水，未处理对照组（N = 20）不注射。实验组的动物在第3天、第6天和第10天被处死。采集颊囊进行组织学和组织化学评估。发育异常在组织学上从0到4级进行分级。对组织学数据的统计分析显示，无论是处死日期还是组别，均无显著差异。通过对γ-谷氨酰转肽酶（GGT，发育异常细胞集落的标志物）染色进行组织化学评估，结果显示实验组中GGT阳性细胞的密度与基线水平有显著差异。实验组之间未检测到显著差异。GGT阳性细胞的密度与发育异常的组织学分级之间相关性较差。得出的结论是，在这个地鼠模型中，暴露于PDGF-BB和IGF-1对上皮发育异常没有明显影响。
