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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.
AuthorsJ K Dunnick, J M Sanders, G E Kissling, C L Johnson, M H Boyle, S A Elmore
JournalToxicologic pathology (Toxicol Pathol) Vol. 43 Issue 4 Pg. 464-73 (Jun 2015) ISSN: 1533-1601 [Electronic] United States
PMID25476797 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Review)
Copyright© 2014 by The Author(s).
Chemical References
  • Carcinogens
  • Environmental Pollutants
  • Polybrominated Biphenyls
  • tetrabromobisphenol A
Topics
  • Animals
  • Body Weight (drug effects)
  • Carcinogenicity Tests
  • Carcinogens (toxicity)
  • Environmental Pollutants (toxicity)
  • Female
  • Polybrominated Biphenyls (toxicity)
  • Uterine Neoplasms (chemically induced, pathology)
  • Uterus (drug effects, pathology)

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