Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice
| Autor: | Bruce Alex Merrick, Grace E. Kissling, Esra Mutlu, Amy E. Brix, Arun R. Pandiri, T. V. Ton, Helen Cunny, Suramya Waidyanatha, Hue-Hua L. Hong, Michael J. DeVito, Leslie Recio, Suzanne L. Phillips, Timothy Maynor, Robert C. Sills, June K. Dunnick |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pituitary gland medicine.medical_specialty Stromal cell Liver toxicity Health Toxicology and Mutagenesis Uterus 010501 environmental sciences Biology Toxicology 01 natural sciences Article 03 medical and health sciences lcsh:RA1190-1270 Internal medicine medicine Carcinogen ComputingMethodologies_COMPUTERGRAPHICS lcsh:Toxicology. Poisons 0105 earth and related environmental sciences Carcinogenic activity Pentabrominated diphenyl ethers Thyroid Cancer medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology In utero Hormone |
| Zdroj: | Toxicology Reports, Vol 5, Iss, Pp 615-624 (2018) Toxicology Reports |
| ISSN: | 2214-7500 |
| DOI: | 10.1016/j.toxrep.2018.05.010 |
| Popis: | Graphical abstract Highlights • Pentabrominated diphenyl ether (PBDE) mixture was a multispecies carcinogen causing liver tumors in male and female rats and mice. • Hras or Ctnnb1 mutations characterized the PBDE-induced liver tumors. • PBDE-induced liver tumors increased with increasing PBDE exposure. Pentabrominated diphenyl ether (PBDE) flame retardants have been phased out in Europe and in the United States, but these lipid soluble chemicals persist in the environment and are found human and animal tissues. PBDEs have limited genotoxic activity. However, in a 2-year cancer study of a PBDE mixture (DE-71) (0, 3, 15, or 50 mg/kg (rats); 0, 3, 30, or 100 mg/kg (mice)) there were treatment-related liver tumors in male and female Wistar Han rats [Crl:WI(Han) after in utero/postnatal/adult exposure, and in male and female B6C3F1 mice, after adult exposure. In addition, there was evidence for a treatment-related carcinogenic effect in the thyroid and pituitary gland tumor in male rats, and in the uterus (stromal polyps/stromal sarcomas) in female rats. The treatment-related liver tumors in female rats were unrelated to the AhR genotype status, and occurred in animals with wild, mutant, or heterozygous Ah receptor. The liver tumors in rats and mice had treatment-related Hras and Ctnnb mutations, respectively. The PBDE carcinogenic activity could be related to oxidative damage, disruption of hormone homeostasis, and molecular and epigenetic changes in target tissue. Further work is needed to compare the PBDE toxic effects in rodents and humans. |
| Databáze: | OpenAIRE |
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