Abstract 1583: Western diet enhances benzo(a)pyrene [B(a)P]-induced colon tumorigenesis in the PIRC rat model via proinflammatory mechanisms

Abstract

Abstract Colorectal cancer ranks third in terms of mortalities in the United States. Consumption of Western Diet (rich in red meat and fats), contaminated with environmental toxicants such as benzo(a)pyrene [B(a)P] has also been implicated as one of the causative factors for sporadic colon cancer. Therefore, the objective of this study was to investigate the effect of dietary fat type on B(a)P -induced colon cancer in an adult male rat model, the Polyposis In the Rat Colon (PIRC) kindred type. Groups of PIRC rats (n = 5) were fed with AIN-76A regular diet (RD) or Western diet (WD) and these rats also received 25, 50 and 100 µg B(a)P/kg body wt., daily via oral gavage for a period of 60 days. Rats that were fed with the diets alone, but no B(a)P served as controls. Food consumption and body weights of the rats were periodically monitored. Subsequent to exposure, rats were sacrificed; colons, liver and other tissues were retrieved and preserved in 10% formalin for observation of gross pathological changes. Blood samples were collected and concentrations of cholesterol, triglycerides, and adiponectin were measured. Colon tissues were scored for tumors, and preserved in 10% formalin for observation of pathological changes. Colon and liver samples were analyzed for activation of drug metabolizing enzymes (DMEs) CYP1A1, CYP1B1 and GST. The lack of change in food consumption notwithstanding, body weight loss of WD group compared to RD group and controls (p < 0.05) was noticed. An increased incidence of adenomas and high grade dysplasia were encountered in rats that were fed with WD compared to RD and controls (p < 0.05). The colon tumor counts were more in B(a)P + WD rats compared to their B(a)P + RD counterparts, and also exhibited a B(a)P dose-response relationship, with 100 µg B(a)P/kg registering greater counts. Adenomas with high grade dysplasia were prominent in B(a)P + WD rats compared to B(a)P + RD rats. Immunohistochemical analyses of colon tissue samples for PCNA, cyclin D1, TGF-β, and β-catenin revealed increased levels of cell proliferation and nuclear positivity among all treatment groups. Rats that received B(a)P + WD showed increased levels of cholesterol and triglycerides in comparison to rats that received B(a)P + RD and also controls. Levels of adiponectin did not vary much between B(a)P + WD, and B(a)P + RD groups. Western diet consumption increased DME activation among rats that were given B(a)P + WD with marked increase in rats that were administered 100 µg/kg B(a)P + WD (p < 0.05) compared to other treatment groups. Our results demonstrate that WD accelerates the development of colon tumors induced by B(a)P through proinflammatory action, characterized by gain in tumor number and sizes, and body weight loss. Citation Format: Kelly L. Harris, Stephanie R. Pulliam, Mohammad S. Niaz, Mary K. Washington, Samuel E. Adunyah, Aramandla Ramesh. Western diet enhances benzo(a)pyrene [B(a)P]-induced colon tumorigenesis in the PIRC rat model via proinflammatory mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1583. doi:10.1158/1538-7445.AM2014-1583