Gingival Changes in Wistar Rats after Oral Treatment with 4-Nitroquinoline 1-Oxide

ABSTRACT

Objectives:4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. However, gingival changes following 4NQO administration via drinking water are absent in the literature. The aim of this study was to investigate gingival changes concomitant to tongue carcinogenesis induced by 4NQO by means of morphological analysis.

Methods:Male Wistar rats were distributed into 3 groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Thirty animals were used as negative control.

Results: Regarding tongue mucosa, the primary histopathological change i.e., hyperplasia and dysplasia was evidenced after 12 weeks treatment with 4NQO. At 20 weeks, squamous cell carcinoma was found in the majority of animals. Gingival squamous hyperplasia was induced by 4NQO after 20-weeks of treatment. Dysplastic changes appeared in some animals (two cases) as well.

Conclusions:Taken together, our results support the notion that 4NQO is more effective in rat tongue mucosa than gingival tissue. Probably, this discrepancy depends strongly on route of administration and the susceptibility with respect to animals species. Certainly, such data will contribute when using this experimental test-system for understanding oral cancer pathogenesis. (Eur J Dent 2007;1:152-157)

Key words

Oral cancer - 4-nitroquinoline 1-oxide - Rat - Gingiva

• References

• 1 Magrath I, Litvak J. Cancer in developing countries: opportunity and challenge. J Natl Cancer Inst 1993; 85: 862-874
• 2 Xi S, Grandis JR. Gene therapy for the treatment of oral squamous cell carcinoma. J Dent Res 2003; 82: 011-016
• 3 Hahn M, Hagedorn G, Kuhlisch E, Schackert HK, Edkelt U. Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to oral cavity cancer. Oral Oncol 2002; 38: 486-490
• 4 Kitakawa D, Cabral LAG, Marques ME, Salvadori DM, Ribeiro DA. Medium-term tongue carcinogenesis assays: a comparative study between 4-nitroquinoline 1-oxide (4NQO) induced rat and dimethylbenzanthracene (DMBA) induced hamster carcinogenesis. J Exp Animal Sci 2006; 43: 219-227
• 5 Tanaka T, Kohno H, Sakata K, Yamada Y, Hirose Y, Sugie S, Mori H. Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Carcinogenesis 2002; 23: 1361-1367
• 6 Ohne M, Satoh T, Yamada S, Takai H. Experimental tongue carcinoma of rats induced by oral administration of 4-nitroquinoline 1-oxide (4NQO) in drinking water. Oral Surg Oral Med Oral Pathol 1985; 59: 600-607
• 7 Nishimura A. Changes in Bcl-2 and Bax expression in rat tongue during 4-nitroquinoline 1-oxide-induced carcinogenesis. J Dent Res 1999; 78: 1264-1269
• 8 Niwa S, Ueno S, Shirasu R. Alteration of pRB expression in the development of rat tongue carcinoma induced by 4- nitroquinoline 1-oxide. Oral Oncol 2001; 37: 579-585
• 9 Okazaki Y, Tanaka Y, Tonogi M, Yamane G. Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia. Oral Oncol 2002; 38: 562-573
• 10 Vered M, Daniel N, Hirshberg A, Dayan D. Histomorphologic and morphometric changes in minor salivary glands of the rat tongue during 4-nitroquinoline 1-oxide-induced carcinogenesis. Oral Oncol 2003; 39: 491-496
• 11 Tang XH, Knudsen B, Benis D, Tickoo S, Gudas LJ. Oral cavity and esophageal carcinogenesis modeled in carcinogentreated mice. Clin Cancer Res 2004; 10: 301-303
• 12 Kramer IR, Lucas RB, Pindbord JJ. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978; 46: 518-539
• 13 Nauta JM, Roodenberg JLN, NIkkels PGJ, Witjes MJH, Vermey A. Comparison of epithelial dysplasia – the 4NQO rat palate model and human oral mucosa. Int J Oral Maxillofac Surg 1995; 24: 053-058
• 14 Ribeiro DA, Silva RN, Darros BR, Salvadori DM, Marques ME. Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide induced rat tongue carcinogenesis. Oral Oncol 2004; 40: 910-915
• 15 Ribeiro DA, Salvadori DM, Marques ME. Abnormal expression of bcl-2 and bax during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. Int J Exp Pathol 2005; 86: 375-381
• 16 Neville Neville, Brad W, Damm Damm, Douglas D. Patologia Oral & Maxilofacial [in Portuguese] 2nd Ed. Guanabara Koogan; Rio de Janeiro: 2004: 0
• 17 Brunet L, Miranda J, Farre M, Berini L, Mendieta C. Gingival enlargement induced by drugs. Drug Saf 1996; 15: 219-231
• 18 Haschek WM, Rousseaux CG. Oral mucosa. In: Fundamentals of Toxicology Pathology. Academic Press, San Diego. 1998; 0
• 19 Ten Cate AR. Oral Histology: development, structure and function. 5th ed. Mosby-Year book Inc; St Louis, USA: 1998: 0
• 20 Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharmaceut Sci 1998; 1: 015-030
• 21 Shimono M, Ishikawa TJ, Enokiya YM, Muramatsu T, Matsuzaka K, Inoue T, Abiko Y, Yamaza T, Kido MA, Tanaka T, Hashimoto S. Biological characteristics of the junction epithelium. J Electron Microsc 2003; 52: 627-639
• 22 Watanabe K, Petro BJ, Sevandal M, Anshuman S, Jovanovic A, Tyner AL. Tyner AL. Histochemical examination of periodontal junctional epithelium in p21/p27 double knockout mice. Eur J Oral Sci 2004; 112: 253-258
• 23 Vondracek M, Xi Z, Larsson P, Baker V, Mace K, Pfeifer A, Tjalve H, Donato MJ, Gomez-Lechon MJ, Grafstrom RC. Cytochrome P450 expression and related metabolism in human buccal mucosa. Carcinogenesis 2001; 22: 481-488