Biomonitoring of mutagenicity and cytotoxicity in patients undergoing fixed orthodontic therapy Fernanda Angelieri, a Viviane Carlin, b Renato A. Martins, c and Daniel A. Ribeiro b,d S~ ao Paulo, Brazil Introduction: The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated buccal mucosa cells from adults after fixed orthodontic ther- apy. Material and Methods: A total of 23 healthy adults (10 men and 13 women) undergoing orthodontic therapy were included in this setting. Results: The results pointed out no significant statistically differences (P .0.05) of micronucleated oral mucosa cells. In the same way, orthodontic therapy was not able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis and karyolysis (P .0.05). Conclusion: In summary, these data indicate that orthodontic therapy may not be a factor that induces chromosomal damage, nor it is able to promote cytotoxicity. Since DNA damage and cellular death are important events during carci- nogenic processes, especially in early phases, this study represents a correct evaluation with respect to real health risks induced by orthodontic devices. (Am J Orthod Dentofacial Orthop 2011;139:e399-e404) E nvironmental health sciences focus on the link be- tween the presence of contaminants in the envi- ronment and their relation to possible adverse health effects. Within this context, human biomonitor- ing data have proved to be a valuable addition to, or have even surpassed, estimates of exposure based on en- vironmental measures. 1 Particularly, biomonitoring of human populations exposed to potential mutagens, cy- totoxins, or even carcinogens can provide an early detec- tion system for the initiation of cell deregulation in the development of cancer. 2 As a result, several markers have been identified to monitor the exposure of humans to mutagens and carcinogens. Classically, mutagenicity tests evaluate chromosomal aberration and sister chro- matid exchange. Data are accumulating that support the hypothesis that mutagenicity end points are predic- tors of human cancer risk. However, the relationship among DNA damage, persistence and repair, and muta- genic end points remains complex. 2 Intraoral fixed orthodontic appliances include brackets, bands, and arch wires that are made of alloys containing nickel, cobalt, and chromium in different percentages. Actually, different types of orthodontic brackets are available in the global market. The number of bracket systems for orthodontic therapy has increased significantly. In a previous study conducted by Faccioni et al 3 , it was found that, as assessed by the single-cell gel (comet) assay in human patients, orthodontic therapy can induce DNA damage in oral mucosa cells as a result of nickel and cobalt released from fixed orthodontic ap- pliances. The alkaline version of the single-cell gel (comet) assay is sensitive for a wide variety of DNA le- sions. Among them are single strand and double strand breaks; oxidative DNA base damage; alkali-labile sites, including abasic and incomplete repair sites; and DNA- DNA/DNA-protein/DNA-drug cross-linking in any eu- karyotic cell. 4 However, the single-cell gel (comet) assay does not necessarily predict the mutagenic potential of metals; moreover, the genotoxicity can be modulated in combination with other DNA-damaging agents that are present in the environment. 5 This is because the ab- sence of a close relationship between DNA migration in the comet assay and mutagenesis may be explained by the fact that some effects seen in the comet assay occur as a consequence of an error-free DNA repair process. 6 Herein, further evaluation of orthodontic therapy and a Associate professor, Department of Orthodontics, S~ ao Paulo Methodist Univer- sity, S~ ao Bernardo do Campo, SP, Brazil. b Graduate student, Department of Pathology, Paulista Medical School, Federal University of S~ ao Paulo, SP, Brazil. c Undergraduate student, Department of Biosciences, Federal University of S~ ao Paulo, Santos, SP, Brazil. d Professor, Department of Pathology, Paulista Medical School, Federal University of S~ ao Paulo, SP, Brazil; Department of Biosciences, Federal University of S~ ao Paulo, Santos, SP, Brazil. The authors report no commercial, proprietary, or financial interest in the prod- ucts or companies described in this article. This study was supported by grants from S~ ao Paulo Research Foundation (Grant number: 07/00345-7). R.A.M. is a recipient of the S~ ao Paulo Research Foundation’s student fellowship and D.A.R. is a recipient of the CNPq fellowship. Reprint requests to: Daniel Araki Ribeiro, Departamento de Biociencias Universidade Federal de S~ ao Paulo – UNIFESP, Av. Ana Costa 95, 11060-001, Santos – SP, Brazil; e-mail, daribeiro@unifesp.br; daribeiro@pesquisador.cnpq.br. Submitted, May 2009; revised and accepted, June 2009. 0889-5406/$36.00 Copyright Ó 2011 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2009.06.029 e399 ONLINE ONLY