Hepatic gene expression analysis of 2-aminoanthracene exposed Fisher-344 rats reveal patterns indicative of liver carcinoma and type 2 diabetes

Abstract

-The goal of the present study was to examine hepatic differential gene expression patterns in Fisher-344 rats in response to dietary 2-aminoanthracene (2AA) ingestion for 14 and 28 days. Twenty four post-weaning 3-4 week old F-344 male rats were exposed to 0 mgkg -1 -diet (control), 50 mgkg -1 -diet (low dose), 75 mgkg -1 -diet (medium dose) and 100 mgkg -1 -diet (high dose) 2AA for 14 and 28 days. This was followed by analysis of the liver for global gene expression changes. In both time points, the numbers of genes affected seem to correlate with the dose of 2AA. Sixteen mRNAs were differentially expressed in all treatment groups for the short-term exposure group. Similarly, 51 genes were commonly expressed in all 28-day exposure group. Almost all the genes seem to have higher expression relative to the controls. In contrast, cytochrome P450 family 4, subfamily a, polypeptide 8 (Cyp4a8), and monocyte to macrophage differentiation-associated (Mmd2) were down-regulated relative to controls. Differentially expressed mRNAs were further analyzed for associations via DAVID. GO categories show the effect of 2AA to be linked with genes responsible for carbohydrate utilization and transport, lipid metabolic processes, stress responses such as inflammation and apoptosis processes, immune system response, DNA damage response, cancer processes and circadian rhythm. The data from the current study identified altered hepatic gene expression profiles that may be associated with carcinoma, autoimmune response, and/or type 2 diabetes. Possible biomarkers due to 2AA toxicity in the liver for future study include Abcb1a, Nhej1, Adam8, Cdkn1a, Mgmt, and Nrcam.

Genetic dissection of the fatty liver QTL Fl1sa by using congenic mice and identification of candidate genes in the liver and epididymal fat

“…Nrcam is a neuronal cell adhesion molecule that mediates neuron-neuron and neuron-glia adhesion [18]. Furthermore, it was reported that Nrcam was induced in the liver of Fisher-344 rats fed 2-aminoanthracene [19]. Further investigation is needed to clarify the functions of these two genes in lipid metabolism.…”

Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response toIn UteroPolycyclic Aromatic Hydrocarbons Exposure

“…2AA is categorized as a polycyclic aromatic hydrocarbon (PAH) and as an arylamine [2728]. 2AA can be found throughout the environment, including broiled food and tobacco smoke, as well as in a wide range of products, including coal, tar, crude oil, cereals, grains, flour, vegetables, and pickled foods.…”

Time-dependent regulation of apoptosis by aen and bax in response to 2-Aminoanthracene dietary consumption

“…Incomplete combustion of fuel, pyrolysis of fossil fuels, and wood and industrial emissions are other sources of PAHs. [12] The Agency for Toxic Substance and Disease Registry (ATSDR) has designated anthracene along with others such as pyrene and phenanthrene as priority PAHs due to their harmful effects, which are representative of other PAHs. Moreover, these PAHs and associated analogs seem to be more harmful, have greater environmental concentration, and present the greatest exposure possibilities.…”

“…Global gene expression patterns in the liver[2] and pancreas[8] of Fisher-344 (F344) rats’ response to 2AA dietary consumption were previously examined. Differentially expressed transcripts in the pancreas showed proteins to be involved in energy metabolism and protein digestion.…”

“…Further analysis via association bioinformatics tool confirmed that biological process and molecular functions related to apoptosis and apoptotic processes are important aspects of 2AA toxicity responses. [2]…”