Suppressive effects of a selective cyclooxygenase-2 inhibitor, etodolac, on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2004-12, Vol.56 (3), p.145-151
• Main Authors: Yamamoto, K., Kitayama, W., Denda, A., Morisaki, A., Kuniyasu, H., Inoue, M., Kirita, T.
• Format: Article
• Language: English
• Subjects: 4-nitroquinoline 1-oxide; 4-Nitroquinoline-1-oxide - toxicity; Administration, Oral; Animals; Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Carcinogens - toxicity; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - prevention & control; Chemoprevention; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase-2; Disease Models, Animal; Dose-Response Relationship, Drug; Etodolac; Etodolac - administration & dosage; Etodolac - pharmacology; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Precancerous Conditions - chemically induced; Precancerous Conditions - pathology; Precancerous Conditions - prevention & control; Quinolones - toxicity; Rat; Rats; Rats, Inbred F344; Tongue - drug effects; Tongue - enzymology; Tongue Neoplasms - chemically induced; Tongue Neoplasms - pathology; Tongue Neoplasms - prevention & control; Tongue tumor; Water Supply
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2004.07.001

The present study was conducted to examine effects of a clinically available selective cyclooxygenase (COX)-2 inhibitor, etodolac, on the development of rat tongue squamous cell carcinomas (SCCs) induced by 4-nitroquinoline 1-oxide (4-NQO), and on the immunohistochemically demonstrable expression of COX-2. Fischer 344 rats, 6 weeks old at the commencement, were administered 4-NQO at the doses of 20–30 ppm in their drinking water for 12 weeks. Then, etodolac was supplemented into the diet at doses of 150 and 300 ppm for 16 weeks. Rats were sacrificed at 28 weeks and tongue lesions were histologically examined. The incidence and the multiplicity of SCCs induced by 4-NQO were dose-dependently reduced by etodolac, with significance at the highest dose of 300 ppm. Etodolac did not significantly affect the immunohistochemical expression of COX-2 in the lesions which did develop. These results indicate that etodolac can inhibit the development of rat tongue SCCs, probably by inhibiting COX-2 activity rather than its expression. Thus, etodolac may be a promising candidate chemopreventive agent for individuals at high risk of oral cancer.