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Induction of apoptosis in rabbit oral mucosa by 1.23% acidulated phosphate fluoride gel

  • Organ Toxicity and Mechanisms
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Abstract

Applying of 1.23% acidulated phosphate fluoride (APF) gel to prevent caries in children has become very popular among dental practitioners. When applied to dental surfaces, however, APF often comes into contact with the oral mucosa. Due to the possibility of local toxic effect, we aimed to investigate the effects of APF on rabbit oral mucosa. Rabbits were sacrificed 1, 5 and 8 days after topical application of 1.23% APF on the oral buccal mucosa for 4 min. The nuclei with DNA strand breaks of the basal epithelial cell layer was estimated using terminal-deoxynucleotidyl-transferase-mediated deoxyuridine-triphospate-biotin nick end labeling (TUNEL). Epithelial cells were analyzed by transmission electron microscopy. The number of basal epithelial cells with DNA strand breaks increased with time in rabbits treated with 1.23% APF. Transmission electron microscopy revealed evidence of apoptosis in the parabasal and basal epithelial cells showed, with loss of cell-to-cell contact, nuclear chromatin condensation and apoptotic bodies. The results demonstrate in vivo that 1.23% APF induced apoptosis in basal epithelial cells of rabbit oral mucosa. It suggests the possible necessity to prevent oral mucosa contact when APF applied on teeth.

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Abbreviations

APF:

Acidulated phosphate fluoride

TUNEL:

Terminal-deoxynucleotidyl-transferase-mediated deoxyuridine-triphospate-biotin nick end labeling

TEM:

Transmission electron microscopy

PTD:

Probably toxic dose

TdT:

Terminal deoxynucleotidyl transferase

References

  • Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326

    Article  PubMed  CAS  Google Scholar 

  • Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1944) Differentiated cells and the maintenance of tissues. Garland Publishing, New York

    Google Scholar 

  • Anuradha CD, Kanno S, Hirano S (2001) Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells. Free Radic Biol Med 31:367–373

    Article  PubMed  CAS  Google Scholar 

  • Branemark PI (1967) Local tissue effects of sodium fluoride. Odontol Revy 18:273–294

    PubMed  CAS  Google Scholar 

  • Burlacu A (2003) Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med 7:249–257

    Article  PubMed  CAS  Google Scholar 

  • Charriaut-Marlangue C, Ben-Ari Y (1995) A cautionary note on the use of the TUNEL stain to determine apoptosis. Neuroreport 7:61–64

    PubMed  CAS  Google Scholar 

  • Duckworth RM, Morgan SN (1991) Oral fluoride retention after use of fluoride dentifrices. Caries Res 25:123–129

    Article  PubMed  CAS  Google Scholar 

  • Eichmiller FC, Eidelman N, Carey CM (2005) Controlling the fluoride dosage in a patient with compromised salivary function. J Am Dent Assoc 136:67–70; quiz 91

    PubMed  Google Scholar 

  • Gabler WL (1968) Absorption of fluoride through the oral mucosa of rats. Arch Oral Biol 13:619–623

    Article  PubMed  CAS  Google Scholar 

  • Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501

    Article  PubMed  CAS  Google Scholar 

  • Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21:1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Harris NO, Garcia-Godoy F (1999) Primary preventive dentistry. Appleton & Lange, Connecticut

    Google Scholar 

  • Hawkins R, Locker D, Noble J, Kay EJ (2003) Prevention. Part 7 professionally applied topical fluorides for caries prevention. Br Dent J 195:313–317

    Article  PubMed  CAS  Google Scholar 

  • Hume WR, Yoon NA, Matsunaga ML (1981) Comparison of fluoride toxicity between periodontal pathogenic bacteria and rabbit gingiva. Arch Oral Biol 26:467–472

    Article  PubMed  CAS  Google Scholar 

  • Jeng JH, Hsieh CC, Lan WH, Chang MC, Lin SK, Hahn LJ, Kuo MY (1998) Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms. Cell Biol Toxicol 14:383–389

    Article  PubMed  CAS  Google Scholar 

  • Kressel M, Groscurth P (1994) Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res 278:549–556

    PubMed  CAS  Google Scholar 

  • LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, Fong S, Schwall R, Sinicropi D, Ashkenazi A (2002) Tumor-cell resistance to death receptor–induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 8:274–281

    Article  PubMed  CAS  Google Scholar 

  • Lecompte EJ (1987) Clinical application of topical fluoride products-risks, benefits, and recommendations. J Dent Res 66:1066–1071

    PubMed  CAS  Google Scholar 

  • LeCompte EJ, Doyle TE (1982) Oral fluoride retention following various topical application techniques in children. J Dent Res 61:1397–1400

    PubMed  CAS  Google Scholar 

  • LeCompte EJ, Whitford GM (1981) The biologic availability of fluoride from alginate impressions and APF gel applications in children. J Dent Res 60:776–780

    PubMed  CAS  Google Scholar 

  • LeCompte EJ, Whitford GM (1982) Pharmacokinetics of fluoride from APF gel and fluoride tablets in children. J Dent Res 61:469–472

    PubMed  CAS  Google Scholar 

  • Marinho VC, Higgins JP, Logan S, Sheiham A (2003) Systematic review of controlled trials on the effectiveness of fluoride gels for the prevention of dental caries in children. J Dent Educ 67:448–458

    PubMed  Google Scholar 

  • Olivier M, Brodeur JM, Simard PL (1992) Efficacy of APF treatments without prior toothcleaning targeted to high-risk children. Community Dent Oral Epidemiol 20:38–42

    Article  PubMed  CAS  Google Scholar 

  • Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619

    Article  PubMed  CAS  Google Scholar 

  • Otsuki S, Morshed SR, Chowdhury SA, Takayama F, Satoh T, Hashimoto K, Sugiyama K, Amano O, Yasui T, Yokote Y, Akahane K, Sakagami H (2005) Possible link between glycolysis and apoptosis induced by sodium fluoride. J Dent Res 84:919–923

    Article  PubMed  CAS  Google Scholar 

  • Sen BH, Kazemi RB, Spangberg LS (1998) Morphologic effects on L929 fibroblasts of titanium tetrafluoride application. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:341–346

    Article  PubMed  CAS  Google Scholar 

  • Sjostrom S, Kalfas S (1999) Tissue necrosis after subgingival irrigation with fluoride solution. J Clin Periodontol 26:257–260

    Article  PubMed  CAS  Google Scholar 

  • Sloop GD, Roa JC, Delgado AG, Balart JT, Hines MO III, Hill JM (1999) Histologic sectioning produces TUNEL reactivity. A potential cause of false-positive staining. Arch Pathol Lab Med 123:529–532

    PubMed  CAS  Google Scholar 

  • Swieterman RM, Muhler JC, Swenson HM (1961) The effect of highly concentrated solutions of stannous fluoride on human gingival tissue. J Periodontol 32:131–138

    CAS  Google Scholar 

  • van Rijkom HM, Truin GJ, van ‘t Hof MA (2004) Caries-inhibiting effect of professional fluoride gel application in low-caries children initially aged 4.5–6.5 years. Caries Res 38:115–123

    Article  PubMed  CAS  Google Scholar 

  • Whitford GM (1990) The physiological and toxicological characteristics of fluoride. J Dent Res 69(Spec No):539–549; discussion 556–537

    PubMed  CAS  Google Scholar 

  • Xu H, Zhang JM, Zhang XY, Li GS (2005) Differential expression of osteopontin and bax, bcl-2 by fluoride. Zhonghua Yu Fang Yi Xue Za Zhi 39:107–110

    PubMed  CAS  Google Scholar 

  • Xu H, Jin XQ, Jing L, Li GS (2006) Effect of sodium fluoride on the expression of bcl-2 family and osteopontin in rat renal tubular cells. Biol Trace Elem Res 109:55–60

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Dr. WenChieh Chen for his kind help in consultation of dermatology. This investigation was supported in part by CMRP Research Grant from the Chang Gung Memorial Hospital, Kaohsiung, Taiwan (CMRPG 84033 to CL Tsai).

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Authors and Affiliations

  1. Department of Pediatric Dentistry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Chia-Ling Tsai

  2. Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Jui-Wei Lin

  3. Department of Ophthalmology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Hsi-Kung Kuo, Yi-Chen Wu & Pei-Chang Wu

  4. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ming-Hong Tai & Pei-Chang Wu

  5. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Ming-Hong Tai

  6. School of Traditional Chinese Medicine, Chang Gung University, Tao-Yuan, Taiwan

    Chih-Rong Shyr

  7. 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, 883, Taiwan, ROC

    Pei-Chang Wu

Authors
  1. Chia-Ling Tsai
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  2. Jui-Wei Lin
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  3. Hsi-Kung Kuo
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  4. Ming-Hong Tai
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  5. Yi-Chen Wu
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  7. Pei-Chang Wu
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Corresponding author

Correspondence to Pei-Chang Wu.

Additional information

This work has been presented in the international congress of 20th International Association of Pediatric Dentistry (IAPD) in Sydney, Australia.

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Tsai, CL., Lin, JW., Kuo, HK. et al. Induction of apoptosis in rabbit oral mucosa by 1.23% acidulated phosphate fluoride gel. Arch Toxicol 82, 81–87 (2008). https://doi.org/10.1007/s00204-007-0239-9

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  • DOI: https://doi.org/10.1007/s00204-007-0239-9

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