The effects of platelet-derived growth factor-BB and insulin-like growth factor-1 on epithelial dysplasia.
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.
Shih
S D
SD
Department of Periodontology, Harvard School of Dental Medicine, Boston, MA, USA.
Rees
T D
TD
Miller
E G
EG
Wright
J M
JM
Iacopino
A M
AM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000704:Analysis of Variance; D000818:Animals; D000077214:Becaplermin; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002610:Cheek; D016009:Chi-Square Distribution; D006224:Cricetinae; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006133:Growth Substances / Q000633:toxicity*; D006651:Histocytochemistry; D007334:Insulin-Like Growth Factor I / Q000633:toxicity*; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology; D009062:Mouth Neoplasms / Q000139:chemically induced*; D010982:Platelet-Derived Growth Factor / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced*; D020574:Proto-Oncogene Proteins c-sis; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D005723:gamma-Glutamyltransferase
D014408:Biomarkers, Tumor; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D005723:gamma-Glutamyltransferase