title: 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.
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.
authors.affiliation: Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Micheal P
authors.initials: MP
authors.lastname: Jokinen
authors.forename: Amy E
authors.initials: AE
authors.lastname: Brix
authors.forename: Donald M
authors.initials: DM
authors.lastname: Sells
authors.forename: Tiwanda
authors.initials: T
authors.lastname: Marsh
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wyde
authors.forename: Denise
authors.initials: D
authors.lastname: Orzech
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Haseman
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D004147:Dioxins / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005881:Gingiva / Q000187:drug effects / Q000473:pathology*; D005887:Gingival Neoplasms / Q000139:chemically induced* / Q000473:pathology; D006965:Hyperplasia; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls; C038890:2,3,4,7,8-pentachlorodibenzofuran