Evaluation of the cytotoxic and genotoxic effects of orthodontic bonding adhesives upon human gingival papillae through immunohistochemical expression of p53, p63 and p16.

Abstract. Background: Numerous in vitro studies have shown that composite materials, commonly used for restorations in conservative dentistry, and in orthodontics to anchor brackets to the tooth enamel, have cytotoxic and genotoxic effects. The study determined expression of p53, p63 and p16, biomarkers useful for predicting potential genotoxicity. Patients and Methods: p53, p63 and p16 expression was determined immunohistochemically in the gingival papillae of 99 patients (69 banded orthodontically for at least one year, brackets bonded to teeth with filled flowable composite resin, 30 without orthodontic banding as controls). The papillae samples were removed surgically and examined to evaluate morphological and biological alterations. Results: In no case were morphological alterations visible by microscopy out of the 69 banded patients; four (5.80% ) were positive for p53 and two for p63 expression in the basal and suprabasal layers (2.90% ). One patient was positive for p16 (1.45% ). No control case was positive for any of the biomarkers (0.00% ). Conclusion: The significance of p53, p63 and p16 positivity, and whether these proteins may serve as biomarkers to predict the risk of developing oral lesions (dysplasia, oral cancer) is still unclear. Although details of the mechanisms leading to cell death, genotoxicity and cell-cycle delay are not fully understood, resin monomers may alter cell function in the oral cavity. Numerous in vitro studies have shown that composite materials, in particular some monomeric adhesives used in dentistry, have cytotoxic and genotoxic effects on the cell and it has been established that the co-monomer triethylene glycol dimethacrylate (TEGDMA) causes gene mutations in vitro (1-15). Such materials are commonly used for restorations in conservative dentistry, and in orthodontics to anchor brackets to the dental enamel, the bracket being fixed to the vestibular surface of the tooth. Orthodontic adhesives may be subdivided into the following general categories: hybrid cements; vetroionomeric cements; self-curing resins and light-curing resins. The latter type are in most widespread use. In the first two categories, the polymerization process is activated chemically, while in the case of light-curing resins activation is physical and is produced by light. The polymerization of orthodontic adhesives is never complete (due to the inhibitory effect of the presence of oxygen polymerization remains incomplete at the surface for an approximate thickness of 10-85 μm) (13) and up to 50% of the components do not participate in the reaction. This means that relatively large amounts (up to 14% ) of nonpolymerized and potentially toxic material may be released.