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.