|
| Status |
Public on Dec 02, 2014 |
| Title |
Persistence of furan-induced epigenetic aberrations in the livers of Fisher 344 rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
Furan is a heterocyclic organic compound produced in the chemical manufacturing industry and also found in a broad range of food products, including infant formulas and baby foods. Previous reports have indicated that the adverse biological effects of furan, including its liver tumorigenicity, may be associated with epigenetic abnormalities. In the present study we investigated the persistence of epigenetic alterations in rat liver. Male Fisher 344 (F344) rats were treated by gavage 5 days per week with 8 mg furan/kg body weight (bw)/day for 90 days. After the last treatment, rats were divided randomly into four groups; one group of rats was sacrificed 24 hours after the last treatment, while other groups were maintained without further furan treatment for an additional 90, 180, or 360 days. Treatment with furan for 90 days resulted in alterations in histone lysine methylation and acetylation, oxidative damage to DNA, and changes in the gene expression in the livers. A majority of these furan-induced molecular changes was transient and disappeared after the cessation of furan treatment. In contrast, histone H3 lysine 9, H3 lysine 27, and H3 lysine 56 showed a sustained and time-depended decrease in acetylation, which was associated with formation of heterochromatin and altered gene expression. These results indicate that furan-induced adverse effects may be mechanistically related to sustained changes in histone lysine acetylation that compromise the ability of cells to maintain and control properly the expression of genetic information.
|
| |
|
| Overall design |
Male Fisher 344 (F344) rats were treated by gavage 5 days per week with 8 mg furan/kg body weight (bw)/day for 90 days and gene expression profiles in the livers from four control and four Furan-treated rats were investigated.
|
| |
|
| Contributor(s) |
Tryndyak V, de Conti A, Han T, Fuscoe JC, Beland FA, Doerge DR, Pogribny IP |
| Citation(s) |
25539665 |
| |
| Submission date |
Dec 01, 2014 |
| Last update date |
Jan 22, 2015 |
| Contact name |
Volodymyr Tryndyak |
| E-mail(s) |
volodymyr.tryndyak@fda.hhs.gov
|
| Phone |
870-543-7545
|
| Organization name |
US-FDA National Center for Toxicological Research
|
| Department |
Division of Biochemical Toxicology
|
| Street address |
3900 NCTR Rd
|
| City |
Jefferson |
| ZIP/Postal code |
72079 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL14797 |
Agilent-028279 SurePrint G3 Rat GE 8x60K Microarray (Feature Number version) |
|
| Samples (8)
|
| GSM1556387 |
Male_liver_control_replicate 4 |
| GSM1556388 |
Male_liver_furan_8 mg-kg-day_90 days_replicate 1 |
| GSM1556389 |
Male_liver_furan_8 mg-kg-day_90 days_replicate 2 |
| GSM1556390 |
Male_liver_furan_8 mg-kg-day_90 days_replicate 3 |
| GSM1556391 |
Male_liver_furan_8 mg-kg-day_90 days_replicate 4 |
|
| Relations |
| BioProject |
PRJNA268953 |
Less...
More...