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ToxSci Advance Access originally published online on October 27, 2004
Toxicological Sciences 2005 83(1):64-77; doi:10.1093/toxsci/kfi016
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Toxicological Sciences vol. 83 no. 1 © Society of Toxicology 2005; all rights reserved.

Gingival Carcinogenicity in Female Harlan Sprague-Dawley Rats following Two-Year Oral Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Dioxin-Like Compounds

Katsuhiko Yoshizawa*, Nigel J. Walker{dagger}, Micheal P. Jokinen{ddagger}, Amy E. Brix§, Donald M. Sells, Tiwanda Marsh*, Michael E. Wyde||, Denise Orzech||, Joseph K. Haseman||| and Abraham Nyska*,1

* Laboratory of Experimental Pathology, {dagger} Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; {ddagger} Pathology Associates—A Charles River Company, Durham, North Carolina 27713; § Experimental Pathology Laboratories, Research Triangle Park, North Carolina 27709; Battelle Columbus Laboratories, Columbus, Ohio 43201; and || Toxicology Operations Branch, ||| Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Received September 15, 2004; accepted October 20, 2004

We evaluated gingival toxicities induced by chronic exposure of female Harlan Sprague-Dawley rats to dioxin and dioxin-like compounds (DLCs) and compared them to similarly induced oral lesions reported in the literature. This investigation represents part of an ongoing initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. A full complement of tissues, including the palate with teeth, was examined microscopically. In the groups treated with TCDD and the mixtures of TCDD, PCB126, and PeCDF; PCB126 and 153; and PCB126 and 118, the incidences of gingival squamous hyperplasia increased significantly. Moreover, in the groups treated with TCDD, PCB126, and the mixture of PCB126 and 153, squamous cell carcinoma (SCC) in the oral cavity increased significantly. This investigation constitutes the first report documenting that chronic administration of dioxin-like PCBs can induce gingival SCC in rats. These results indicate that dioxin and DLCs target the gingiva of the oral cavity, in particular the junctional epithelium of molars.

Key Words: gingival squamous hyperplasia; squamous cell carcinoma; rat; dioxin; dioxin-like compounds.


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