Journal of Dental Research, Vol 73, 1043-1049, Copyright © 1994 by International & American Associations for Dental Research Online Journals

ARTICLES

Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro

J. H. Jeng, M. L. Kuo, L. J. Hahn and M. Y. Kuo
School of Dentistry, College of Medicine, National Taiwan University, Taipei, ROC.

To understand the role of betel quid (BQ) in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer, we used DNA damage, cytotoxicity, and cell proliferation assays to study the pathobiological effects of aqueous extracts of three BQ constituents [betel nut (Areca catechu, BN), inflorescence of Piper betle (IPB), and lime], one BN alkaloid (arecoline), and one BN polyphenol [(+)-catechin] on cultured oral mucosal fibroblasts. Extracts of BN and IPB induced DNA strand break formation in a dose-dependent manner. Extracts of BN and IPB, (+)-catechin, and arecoline decreased cell survival and proliferation in a dose-dependent manner. However, aqueous extract of lime (50-800 micrograms/mL) increased cell proliferation by 20-40%. These results indicate that BQ contains not only genotoxic and cytotoxic agents, but also compounds which stimulate cell proliferation. These compounds may act synergistically in the pathogenesis of OSF and oral cancer in BQ chewers. In addition, five anti-oxidants [glutathione (GSH), cysteine, mannitol, catalase, and superoxide dismutase (SOD)] were tested for their protective effects against the cytotoxicity of BQ constituents. GSH (1.95 and 2.6 mmol/L) and cysteine (4 and 8 mmol/L) prevented the arecoline-induced cytotoxicity. In contrast, mannitol, catalase, and SOD did not decrease the arecoline-induced cytotoxicity. These results indicate that thiol depletion, but not the attack of oxygen free radicals, could be the mechanism for arecoline cytotoxicity. GSH could also protect cells from the cytotoxicity of IPB extract. Increasing dietary intake of GSH-rich foods or dietary supplements of GSH may have chemopreventive potential to reduce BQ-associated oral lesions.

This article has been cited by other articles:

				S.-L. Chiang, S.-S. Jiang, Y.-J. Wang, H.-C. Chiang, P.-H. Chen, H.-P. Tu, K.-Y. Ho, Y.-S. Tsai, I-S. Chang, and Y.-C. Ko Characterization of Arecoline-Induced Effects on Cytotoxicity in Normal Human Gingival Fibroblasts by Global Gene Expression Profiling Toxicol. Sci., November 1, 2007; 100(1): 66 - 74. [Abstract] [Full Text] [PDF]

				M.-C. Chang, H.-L. Wu, J.-J. Lee, P.-H. Lee, H.-H. Chang, L.-J. Hahn, B.-R. Lin, Y.-J. Chen, and J.-H. Jeng The Induction of Prostaglandin E2 Production, Interleukin-6 Production, Cell Cycle Arrest, and Cytotoxicity in Primary Oral Keratinocytes and KB Cancer Cells by Areca Nut Ingredients Is Differentially Regulated by MEK/ERK Activation J. Biol. Chem., December 3, 2004; 279(49): 50676 - 50683. [Abstract] [Full Text] [PDF]

				Y.-Y. Yang, L.-W. Koh, J.-H. Tsai, C.-H. Tsai, E. F.-C. Wong, S.-J. Lin, and C.-C. Yang Involvement of Viral and Chemical Factors with Oral Cancer in Taiwan Jpn. J. Clin. Oncol., April 1, 2004; 34(4): 176 - 183. [Abstract] [Full Text] [PDF]

				J. Y.-F. Chen, Y.-L. Chang, Y.-C. Yu, C.-C. Chao, H.-W. Kao, C.-T. Wu, W.-C. Lin, J.-Y. Ko, and Y.-S. Jou Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC) Carcinogenesis, February 1, 2004; 25(2): 269 - 276. [Abstract] [Full Text] [PDF]

				J.-H. Jeng, Y.-J. Wang, B.-L. Chiang, P.-H. Lee, C.-P. Chan, Y.-S. Ho, T.-M. Wang, J.-J. Lee, L.-J. Hahn, and M.-C. Chang Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-{alpha} production of oral epithelial cells by areca nut extract and arecoline Carcinogenesis, August 1, 2003; 24(8): 1301 - 1315. [Abstract] [Full Text] [PDF]

				M.C. Chang, Y.S. Ho, P.H. Lee, C.P. Chan, J.J. Lee, L.J. Hahn, Y.J. Wang, and J.H. Jeng Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential Carcinogenesis, September 1, 2001; 22(9): 1527 - 1535. [Abstract] [Full Text] [PDF]