Western diet enhances benzo(a)pyrene-induced colon tumorigenesis in a polyposis in rat coli (PIRC) rat model of colon cancer

// Kelly L. Harris 1 , Stephanie R. Pulliam 1 , Emmanuel Okoro 2 , Zhongmao Guo 2 , Mary K. Washington 3 , Samuel E. Adunyah 1 , James M. Amos-Landgraf 4 , Aramandla Ramesh 1 1 Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA 2 Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA 3 Department of Pathology, Vanderbilt University, Nashville, TN 37232, USA 4 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA Correspondence to: Aramandla Ramesh, email: aramesh@mmc.edu Keywords: benzo(a)pyrene, colon cancer, PIRC rat, western diet, polyp Received: January 20, 2016      Accepted: February 15, 2016      Published: March 3, 2016 ABSTRACT Consumption of Western diet (WD), contaminated with environmental toxicants, has been implicated as one of the risk factors for sporadic colon cancer. Our earlier studies using a mouse model revealed that compared to unsaturated dietary fat, the saturated dietary fat exacerbated the development of colon tumors caused by B(a)P. The objective of this study was to study how WD potentiates B(a)P-induced colon carcinogenesis in the adult male rats that carry a mutation in the Apc locus - the polyposis in the rat colon (PIRC) rats. Groups of PIRC rats were fed with AIN-76A standard diet (RD) or Western diet (WD) and received 25, 50, or 100 μg B(a)P/kg body weight (wt) via oral gavage for 60 days. Subsequent to exposure, rats were euthanized; colons were retrieved and preserved in 10% formalin for counting the polyp numbers, measuring the polyp size, and histological analyses. Blood samples were collected and concentrations of cholesterol, triglycerides, glucose, insulin and leptin were measured. Rats that received WD + B(a)P showed increased levels of cholesterol, triglycerides, and leptin in comparison to RD + B(a)P groups or controls. The colon tumor numbers showed a B(a)P dose-response relationship. Adenomas with high grade dysplasia were prominent in B(a)P + WD rats compared to B(a)P + RD rats and controls (p < 0.05). The larger rat model system used in this study allows for studying more advanced tumor phenotypes over a longer duration and delineating the role of diet - toxicant interactions in sporadic colon tumor development.