Exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces squamous metaplasia in the endocervix of cynomolgus macaques

Female cynomolgus macaques (n = 11) were treated orally with graded doses o f 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cervical tissue was recovered at necropsy 1.2-2.7 years later and examined using routine histopathology. Results were compared histologically with cervical tissue from untreated, age- and parity-matched controls. Significant squamous epithelial metaplasi a was observed in the endocervix of 9 of 11 TCDD-treated animals, and the d egree of severity was dose dependent. In contrast, minimal or no pathologic al changes were observed in eight of nine control animals and one animal ha d only mild squamous; metaplasia. These results suggest that TCDD exposure induces epithelial transdifferentiation in the primate cervix. Consequently , the TCDD-treated macaque may serve as a predictable animal model for the study of cervical epithelial transdifferentiation and for examining the rel ationship between squamous metaplasia and cervical oncogenesis both at the cellular and at the molecular level.