Metalloproteinase-Disintegrin Adam8: A Potential Biomarker for 2-Aminoanthracene Toxicity in the Liver of Fisher-344 Rats

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Adam8 belongs to a disintegrin and metalloprotease family of genes. This protein has been implicated in a various cellular processes including cell-cell adhesions, muscle development, neurogenesis and asthma. Recently a hepatic global gene expression analysis of the liver was undertaken to identify specific genes that mediate 2-aminoanthracene (2AA) toxicity in the liver. Findings from this study showed Adam8 to be highly expressed in liver tissues of Fisher-344 (F344) rats that consumed dietary 2AA. The goal of the present study was to examine the hepatic expression of Adam8 in F344 rats that ingested 0 mg/kg- (control), 50 mg/kg- (low dose), 75 mg/kg-(medium dose) and 100 mg/kg-diet (high dose) of 2AA for 2 and 4 weeks. The arylamine 2-aminoanthracene (2AA) is an aromatic hydrocarbon employed in manufacturing of chemicals, dyes, inks, and as curing agents in epoxy resins and polyurethanes. 2AA is also present in tobacco smoke as well as over-cooked food. The gene expression of Adam8 was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Adam8 expression in the livers was dose-dependent. This transcript was highly expressed in the high-dose animals of the 2 weeks group. Similar pattern of gene expression was observed in the four weeks group. Relative quantification of Adam8 mRNA was greater in the 2 weeks group than the four weeks set. Specific immunostaining for Adam8 in various tissues has been undertaken with results being analyzed. This will be followed by western blot assay to detect Adam8 protein expression.


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