Rebekah N. Lucier,*† Olivier Etienne,* Susana Ferreira,† Jonathan A. Garlick,* Gerard Kugel,† and Christophe Egles*‡*Department of Oral and Maxillofacial Pathology, Division of Cancer Biology and Tissue Engineering, Tufts University School of Dental Medicine, Boston, MA.†Department of Research Administration, Tufts University School of Dental Medicine.‡Biomécanique et BioIngénierie, UMR-CNRS 7338, Université de Technologie de Compiègne, Compiègne, France.

Correspondence: Prof. Gerard Kugel, Tufts University School of Dental Medicine, Room 1015, 1 Kneeland Street, Boston, MA 02111. Phone: 617/636-0870; fax: 617/636-6511; e-mail: gerard.kugel@tufts.edu.

Background: Tooth-whitening agents are widely used, either as self-application products or under the supervision of a dentist. These products may be associated with transient gross morphologic changes in oral soft tissues. However, their potential effects on human keratinocytes and fibroblasts in a stratified squamous epithelium have yet to be elucidated.

Methods: In this study, three-dimensional human tissue equivalents are exposed to varying concentrations of tooth-whitening agents for increasing time periods. Tissue alterations are investigated in terms of morphology, proliferation, apoptosis, and protein expression.

Results: All whitening agents tested altered tissue morphology, induced proliferation of basal keratinocytes, and caused apoptosis of cells in all epithelial strata. In addition, whitening agents induced alterations in the expression of cytokines that are linked to inflammation.

Conclusions: These results suggest that whitening agents may induce similar changes in vivo and that these products should be used for limited periods of time or under the supervision of a dental professional.

KEYWORDS: Bleaching agents, carbamide peroxide, epithelium, hydrogen peroxide, keratinocytes, toxicity

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