Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water

Toxicol Rep. 2016 Mar 19:3:414-426. doi: 10.1016/j.toxrep.2016.03.009. eCollection 2016.


Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others; animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.

Keywords: ADA, adenosine Deaminase; ADRB2, adrenergic; ASF1B, anti-Silencing Function 1B Histone Chaperone; Acrylamide; BRIP1, BRCA1 Interacting Protein C-Terminal Helicase 1; BUB1B, BUB1 Mitotic Checkpoint Serine/Threonine Kinase B; C1QTNF3, C1q and Tumor Necrosis Factor Related Protein 3; C5, complement Component 5; CALCR, calcitonin receptor; CARD9, caspase recruitment domain family; CCNA2, cyclin A2; CCNG1, cyclin G1; CD45, protein tyrosine phosphatase; CD46, CD46 molecule; CDC45, cell division cycle 45; CDCA2, cell division cycle associated 2; CDCA5, cell division cycle associated 5; CENPT, centromere protein T; CFB, complement factor B; CGA, glycoprotein hormones; CTLA4, cytotoxic T-lymphocyte-associated protein 4; DAD1, defender against cell death 1; DCTPP1, DCTP pyrophosphatase 1; DNMT3A, DNA (cytosine-5-)-methyltransferase 3 alpha; DUOX2, dual oxidase 2; GCG, glucagon; GCLC, glutamate-cysteine ligase; GOLGA3, golgin A3; GSTM1, glutathione S-transferase Mu 1; GSTP1, glutathione S-transferase Pi 1; HPSE, heparanase; HSPA5, heat shock 70 kDa protein 5; HSPB1, heat shock 27 KDa protein; HSPB2, heat shock 27 kDa protein 2; HSPH1, heat shock 105 kDa/110 kDa protein 1; HTATIP2, HIV-1 tat interactive protein 2; ID1, inhibitor of DNA binding 1; IGF2, Insulin-like growth factor 2 (somatomedin A); IL1B, interleukin 1; INHBA, inhibin; IYD, iodotyrosine deiodinase; KIF20B, kinesin family member 20B; KIF22, kinesin family Member 22; KLK1, kallikrein 1; LAMA2, laminin, alpha 2; MCM8, minichromosome maintenance complex component 8; MIF, macrophage migration inhibitory factor; MIS18A, MIS18 kinetochore protein A; NDC80, NDC80 kinetochore complex component; NPPC, natriuretic peptide precursor C; NPY, neuropeptide; NUBP1, nucleotide binding protein 1; ORC1, origin recognition complex; PDE3A, phosphodiesterase 3A; PINK1, PTEN induced putative kinase 1; PLCD1, phospholipase C; PLK1, polo-like kinase 1; POMC, proopiomelanocortin; PRKAA2, protein kinase; PRL, prolactin; PRODH, proline dehydrogenase; PTGIS, prostaglandin I2 (prostacyclin) synthase; PTGS1, prostaglandin-endoperoxide synthase 1; RAB5A, RAB5A; RAN, ras-related nuclear protein; RRM2, ribonucleotide reductase M2; RccHan Wistar; SCL5A5, solute carrier family 5 (sodium iodide symporter); SELP, selectin P (granule membrane protein 140 kDa; SPAG8, sperm associated antigen 8; TACC3, transforming; TBCB, tubulin folding cofactor B; TFRC, transferrin receptor; TOP2A, topoisomerase (DNA) II alpha; TPO, thyroid peroxidase; TSHR, thyroid stimulating hormone receptor; TSN, translin; Thyroid; Transcriptomics; VWF, Von Willebrand Factor.