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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

Battelle Memorial Institute, Columbus, Ohio, United States
Toxicological Sciences (Impact Factor: 4.48). 02/2005; 83(1):64-77. DOI: 10.1093/toxsci/kfi016
Source: PubMed

ABSTRACT 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.

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    • "Exposure to PCB-153 has been reported to cause a wide array of biological effects, such as perturbations of endocrine functions and sex hormone synthesis, reproductive defects, DNA damage, nephro-, immuno-and lung-toxicities (Chen et al., 2006; Craft et al., 2002; Johansson et al., 2006; Jung et al., 2005; Lyche et al., 2006; Oskam et al., 2005; Sipka et al., 2008; Venkatesha et al., 2008). Furthermore, the evidence for liver toxicity, tumor promotion, and oral squamous cell carcinoma formation suggests that PCB-153 exposures could perturb cellular proliferation (Glauert et al., 2008; Strathmann et al., 2006; Yoshizawa et al., 2005). "
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    • "The National Toxicology Program (NTP) recently conducted 2-year bioassays in female rats to evaluate the chronic pathology and carcinogenicity induced by dioxin, DLCs, structurallyrelated PCBs, and mixtures of these compounds, including TCDD; 3,3′,4,4′,5- pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachloro-dibenzifyran (PeCDF); and the Toxic Equivalency Factor (TEF) ternary mixture of TCDD, PCB126, and PeCDF (National Toxicology Program,2004a,b,c,d). In these studies, there was an increase in the incidence of neoplasms and non-neoplastic lesions in several organs notably the liver, lung and oral mucosa (National Toxicology Program, 2004a,b,c,d; Walker et al., 2005, 2006; Hailey et al., 2005; Jokinen et al., 2003; Nyska et al., 2004, 2005; Tani et al., 2004; Yoshizawa et al., 2005a, b). This present article, one of a series of works highlighting specific findings from NTP dioxin- TEF-evaluation studies, focuses on a comparative analysis of pulmonary effects across these studies. "
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    • "— — HSD (TR520) Walker et al., 2005; Yoshizawa et al., 2005a — Squamous hyperplasia/gum swelling/gum pigmentation — HSD (TR521) Yoshizawa et al., 2005a — Asahi, 1993 ATSDR, 1998; Brouwer et al., 1998; Guo et al., 1999, 2004; Hashiguchi et al., 1995, 1997; HSD (TR520) Yoshizawa et al., 2005a — "
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    Toxicologic Pathology 02/2007; 35(7):865-79. DOI:10.1080/01926230701618516 · 1.92 Impact Factor
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