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Characterization of polybrominated diphenyl ether toxicity in Wistar Han rats and use of liver microarray data for
June K Dunnick1, A Brix, H Cunny
1National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. dunnickj@niehs.nih.gov
Insights
Polybrominated diphenyl ethers (PBDEs) altered liver gene expression in developing rats, potentially increasing risks for metabolic disease and cancer. Long-term exposure significantly impacted liver function and cell regulation in offspring.
Area of Science:
- Environmental Toxicology
- Developmental Toxicology
- Molecular Toxicology
Background:
- Polybrominated diphenyl ethers (PBDEs) are flame retardants with known toxicity.
- PBDE exposure during development may impact organ function and long-term health.
- Understanding PBDEs' effects on liver gene expression is crucial for risk assessment.
Purpose of the Study:
- To characterize the toxicity of PBDEs in Wistar Han rat offspring.
- To investigate PBDE-induced changes in liver gene expression from early development through adulthood.
- To assess potential links between PBDE exposure and metabolic or carcinogenic risks.
Main Methods:
- Wistar Han dams were exposed to a PBDE mixture (DE71) from gestation day 6 through weaning.
- Offspring received direct PBDE dosing from postnatal day 12 to week 13.
- Liver gene expression was analyzed using the Affymetrix Rat Genome 230 2.0 Array at postnatal day 22 and week 13.
Main Results:
- PBDE exposure induced significant liver gene expression changes in both male and female pups at postnatal day 22.
- Transcriptional changes at postnatal day 22 involved xenobiotic, lipid, and sterol metabolism, and cell cycle regulation.
- Fewer transcriptional changes were observed at week 13, with no significant sex-based differences in dose response.
Conclusions:
- PBDE exposure significantly alters liver gene expression and function in developing rats.
- Observed changes suggest PBDEs may contribute to metabolic disease and cancer susceptibilities.
- PBDE-induced liver hypertrophy and vacuolization support potential long-term health risks.
Abstract:
The toxicity of polybrominated diphenyl ethers (PBDEs), flame-retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 and continuing to weaning on postnatal day (PND) 21. Offspring from the dams underwent PBDE direct dosing by gavage at the same dose as their dams from PND 12 to PND 21, and then after weaning for another thirteen weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis (Affymetrix Rat Genome 230 2.0 Array). Treatment with PBDE induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate < 0.01), but only 263 liver transcriptional changes at thirteen weeks in male rats (false discovery rate < 0.05). No significant differences in dose response were found between male and female pups. Transcript changes at PND 22 coded for proteins in xenobiotic, sterol, and lipid metabolism, and cell cycle regulation, and overlapped rodent liver transcript patterns after a high-fat diet or phenobarbital exposure. These findings, along with the observed PBDE-induced liver hypertrophy and vacuolization, suggest that long-term PBDE exposure has the potential to modify cell functions that contribute to metabolic disease and/or cancer susceptibilities.
