Dietary Exposure to 2-Aminoanthracene Induces Morphological and Immunocytochemical Changes in Pancreatic Tissues of Fisher-344 Rats

Abstract

Toxic chemicals ingested as the result of environmental exposures or other risk factors such as cigarette smoking may increase the risk of developing cancer and other diseases such as diabetes. 2-Aminoanthracene (2-AA) was investigated to determine toxic effects of chronic dietary exposure upon major organ systems including the pancreas. Fisher-344 rats were fed 2-AA (50-100 mg/kg of diet) and euthanized at 14, 30, 63, and 80 days. Growth, tissue histological, immunocytochemical, and clinical pathological end points were examined at each time point. Significantly elevated plasma glucose and glycated hemoglobins and reduced serum protein levels were recognized after 80 days of feeding (100 mg/kg of diet 2-AA group). Similar results were observed in rats exposed to 75 mg/kg of diet but appeared to be absent in the 50-mg/kg group. An unexpected pattern of responses suggestive of diabetic sequelae was observed in a glucose tolerance test conducted during the seventh week. After 63 and 80 days, large cytoplasmic vacuoles in islet cells were observed by light microscopy. In addition, the immunocytochemical study demonstrated beta cell insulin insufficiency at 63 and 80 days. No inflammatory infiltration of the islets was observed. These findings suggest that depletion of secretory granules occurred in the beta cells. Necrotic changes occurred in the acinar cells of the pancreas with increasing duration and dose of 2-AA. The cytological, immunocytochemical, and histological results demonstrate that chronic dietary exposure to 2-amino anthracene alters the endocrine and exocrine pancreas cellular morphology and induces diabetic-like symptoms in the Fisher-344 rat.

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

“…Analysis of histological, immunocytochemical, and clinical pathological end points showed changes in the endocrine and exocrine pancreas cellular morphology (Boudreau et al, 2006). Similar investigations found pancreatic differentially expressed genes that were involved in energy metabolism in the pancreas, and protein digestion.…”

“…They are employed in the manufacture of dyes, drugs, inks, rubber antioxi-dants, plastics, and agricultural chemicals. These aromatic amines are also used as curing agents in synthesizing epoxy resins and polyurethanes and are found in road tars and synthetic fuels (Boudreau et al, 2006;Snyderwine et al, 1992;Zhu et al, 1995).…”

“…Generally, the liver is also noted as the principal site for xenobiotics metabolism (Shankar and Mehendale, 2010). Boudreau et al (2006) previously investigated the toxicity of 2AA on Fisher-344 rats via immunocytochemical and clinical pathological end points. Results from the study showed changes to the endocrine and exocrine pancreas cellular morphology of the pancreas.…”

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

“…Others have observed that environmental exposures in childhood seem to trigger chronic diseases that affect adults [111213]. Insulin-dependent diabetes mellitus, which results from specific disruption of the pancreatic islet insulin-secreting β-cells, is induced in experimental animals by toxic agents, including chemicals that are byproducts of cigarette smoking [1415]. …”

Energy Transfer Studies between Trp Residues of Three Lipocalin Proteins Family, α1-Acid Glycoprotein, (Orosomucoid), β-Lactoglobulin and Porcine Odorant Binding Protein and the Fluorescent Probe, 1-Aminoanthracene (1-AMA)

“…Fluorophore 1-aminoanthracene (1-AMA) is widely used to study interaction between lipocalin family proteins and their ligands [6][7][8][9][10][11][12]. Aminoanthracene is known to be a cytotoxic compound [13] inducing DNA damaging and thus altering proteins structures.…”