Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure
| Autor: | Sukhdev S. Brar, June K. Dunnick, Kevin Gerrish, Ralph E. Wilson, Esra Mutlu, Daniel L. Morgan, Arun R. Pandiri, Keith R. Shockley, Thai-Vu T. Ton, Amy E. Brix, Gregory S. Travlos, Suramya Waidyanatha |
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| Rok vydání: | 2019 |
| Předmět: |
Male
endocrine system Liver toxicity 010501 environmental sciences Biology Toxicology 01 natural sciences Article Pathology and Forensic Medicine Andrology Transcriptome 03 medical and health sciences chemistry.chemical_compound Pregnancy Lactation Halogenated Diphenyl Ethers medicine Animals Rats Wistar Molecular Biology reproductive and urinary physiology 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Neonatal rat Cell Biology Pentabromodiphenyl ether Rats Congener medicine.anatomical_structure Animals Newborn Liver chemistry Maternal Exposure In utero Human exposure Prenatal Exposure Delayed Effects Female |
| Zdroj: | Toxicol Pathol |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623319888433 |
| Popis: | Human exposure to pentabromodiphenyl ether (PBDE) mixture (DE-71) and its PBDE-47 congener can occur both in utero and during lactation. Here we tested the hypothesis that PBDE-induced neonatal hepatic transcriptomic alterations in Wistar Han rat pups can inform on potential toxicity and carcinogenicity after longer-term PBDE exposures. Wistar Han rat dams were exposed to either DE-71 or PBDE-47 daily from gestation day (GD 6) through postnatal day four (PND 4). Total plasma thyroxine (T4) was decreased in PND 4 pups. In liver, transcripts for CYPs and conjugation enzymes, Nrf2, and ABC transporters were upregulated. In general, the hepatic transcriptomic alterations after exposure to DE-71 or PBDE-47 were similar and provided early indicators of oxidative stress and metabolic alterations, key characteristics of toxicity processes. Based on liver transcript patterns, the mean BMDLs (mean benchmark dose, lower confidence limit) of the most sensitive biological processes were lower for PBDE-47 than for the PBDE mixture. Neonatal rat liver transcriptomic data provide early indicators on molecular pathway alterations that may lead to toxicity and/or carcinogenicity if the exposures continue for longer durations. These early toxicogenomic indicators may be used to help prioritize chemicals for a more complete toxicity and cancer risk evaluation. |
| Databáze: | OpenAIRE |
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