Characterization of Polybrominated Diphenyl Ether Toxicity in Wistar Han Rats and Use of Liver Microarray Data for Predicting Disease Susceptibilities
Dunnick JK, Brix A, Cunny H, Vallant M, Shockley KR.
Toxicol Pathol (2012), DOI: https://doi.org/10.1177/0192623311429973 PMID: 22267650
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.
3 Month Interim of Chronic Study
- P03 - Incidence Rates of Non-Neoplastic Lesions by Anatomic Site (30 KB)
- P04 - Neoplasms by Individual Animal (114 KB)
- P05 - Incidence Rates of Neoplasms by Anatomic Sites (Systemic Lesions Abridged) (31 KB)
- P09 - Non-Neoplastic Lesions by Individual Animal (122 KB)
- P10 - Statistical Analysis of Non-Neoplastic Lesions (111 KB)
- P14 - Individual Animal Pathology Data (199 KB)
- P18 - Incidence Rates of Non-Neoplastic Lesions by Anatomic Site with Average Severity Grades (31 KB)
GEO Series: GSE32156
- DE71 RMA Normalized Data (10 MB)