title: Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A.
abstract: Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17β (HSD17β) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms.
authors.affiliation: National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina, USA dunnickj@niehs.nih.gov.
authors.forename: J K
authors.initials: JK
authors.lastname: Dunnick
authors.affiliation: National Cancer Institute, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Sanders
authors.affiliation: National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: Charles River Laboratories, Pathology Associates, Research Triangle Park, North Carolina, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Johnson
authors.affiliation: Integrated Laboratory Systems, Research Triangle Park, North Carolina, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Boyle
authors.affiliation: National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Elmore
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D002273:Carcinogens; D004785:Environmental Pollutants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A
keywords: flame retardants; malignant mixed Müllerian tumors (MMMT); tetrabromobisphenol A; uterine tumors