-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.

BackgroundIn recent times, there has been an increase in the incidence of type 2 diabetes mellitus (T2DM) particularly in children. Adipocyte dysfunction provide a critical link between obesity and insulin resistance resulting in diabetes outcome. Further, environmental chemical exposure during early years of life might be a significant contributing factor to the increase in the incidence of T2DM. This study tests the idea that exposure to environmental contaminants (2-aminoanthracene [2AA]) in utero will show effects in the adipose tissue (AT) that signify T2DM vulnerability. 2AA is a polycyclic aromatic hydrocarbon found in a variety of products.MethodsTo accomplish the study objective, pregnant dams were fed various amounts of 2AA adulterated diets from gestation through postnatal period. The neonates and older offspring were analyzed for diabetic-like genes in the ATs and analysis of serum glucose. Furthermore, weight monitoring, histopathology and immunohistochemical (IHC) staining for CD68 in AT, adipocyte size determination and adiponectin amounts in serum were undertaken.ResultsUp-regulation of adiponectin and interleukin-6 genes were noted in the pups and older rats. Combination of intrauterine 2AA toxicity with moderate high fat diet exhibited gene expression patterns similar to those of the neonates. Elevated serum glucose levels were noted in treated groups. IHC of the AT indicated no significant malformations; however, CD68+ cells were greater in the animals treated to 2AA. Similarly, mean sizes of the adipocytes were larger in treated and combined 2AA and moderate high fat animals. Adiponectin was reduced in 2AA groups.ConclusionFrom the preceding, it appears intrauterine 2AA disturbance, when combined with excess fat accumulation will lead to greater risk for the diabetic condition.

The percentage of self-reported diabetes in this population was consistent with what has been reported in previous studies in Ghana. The findings from this study highlight the need for more patient education on physical activity and weight management.

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Tin dioxide nanofibers (SnDNFs) are small fibers that have many applications. Tin dioxide nanofibers can be used in cosmetics, solar cells, toxic gas release sensors, and air pollution control. To date there have been few studies on the cytotoxicity of SnDNFs. The goal of this research is to determine if electrospun SnDNFs are toxic in a lung cancer cell line (A549). Considering the nano-scale size of the fibers, they can easily be inhaled and enter the pulmonary system and cause toxic effects in the lung. Occupational exposure to SnDNFs has been linked to pulmonary disease, making the A549 cell line important in this study. Nanofiber toxicity can vary based upon the characteristics of the fibers. Smaller nanofibers have been shown to have more toxic effects than their larger counterparts. The synthesized SnDNFs were characterized using SEM, Raman spectroscopy, and powder X-ray diffractometer (PXRD). SEM images showed the fibers to be 200-300 nm in diameter. Raman spectroscopy and PXRD indicated that the fibers were in the rutile phase. After quantifying the SnDNFs, the fibers were introduced to A549 cells at concentrations ranging from 0.02-500 µg mL and incubated at 37°C. These cells were quantified with the MTT assay to measure cell proliferation (IC = 0.02 mg mL), while lactate dehydrogenase (LDH) leakage was used to determine cytotoxicity, and apoptosis assays to assess the mechanism of cell death. Increasing concentration of SnDNF generated a consequential decrease in cell proliferation and viability. The percent cytotoxicity of SnDNF was not significantly changed at the various concentrations and time frames. In order to gain additional insight about the mechanism of cytotoxicity of SnDNFs, genes with links to inflammation and apoptosis were evaluated and found to be over-expressed in treated cells. At the concentrations of SnDNF examined, SnDNF was mildly toxic to the A549 cells.