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 of 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 metaplasia was observed in the endocervix of 9 of 11 TCDD-treated animals, and the degree of severity was dose dependent. In contrast, minimal or no pathological changes were observed in eight of nine control animals and one animal had 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 relationship between squamous metaplasia and cervical oncogenesis both at the cellular and at the molecular level.
Scott
M A
MA
Institute of Toxicology and Environmental Health, University of California, Davis 95616-8615, USA.
Tarara
R P
RP
Hendrickx
A G
AG
Benirschke
K
K
Overstreet
J W
JW
Lasley
B L
BL
D000284:Administration, Oral; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000503:physiopathology / Q000662:veterinary; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002584:Cervix Uteri / Q000187:drug effects* / Q000473:pathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D008252:Macaca fascicularis; D008679:Metaplasia / Q000139:chemically induced; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced* / Q000503:physiopathology / Q000662:veterinary
D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens