Abstract 1278: Obesity enhances benzo(a)pyrene-induced colon tumorigenesis in a PIRC rat model of colon cancer..

Abstract

Abstract Colorectal cancer is a contributing factor for significant mortalities in the United States, with 50,000 deaths per year and around 140,000 new cases expected to be diagnosed in this year. Epidemiological studies have pointed out that obese people have a higher risk for colon cancer. It is well known that overweight or obesity is induced by excess energy intake from dietary fat. Additionally, consumption of well-done red meat and saturated fats, rich in food-borne environmental toxicants such as polycyclic aromatic hydrocarbons (PAHs) has also been implicated as one of the causative factors for sporadic colon cancer. Thus, on one hand, diet-induced obesity and on the other hand exposures to environmental carcinogens contribute to the development of colon cancer. Therefore, the objective of this study was to investigate whether the colon polyp burden was accelerated by diet-induced obesity when exposed to environmental carcinogens.To test this concept, we have employed an adult male transgenic rat model, the Polyposis In the Rat Colon (PIRC) kindred type. This rat is a mutagen-induced nonsense allele of the rat Apc gene on an inbred F344/NTac (F344) genetic background. This rat model is advantageous because of its longer life span and lack of the tumor suppressor gene Apc. We have explored whether tumor burden in PIRC male rat (PIRC-M Heterozygous F344/NTac-Apcam1137) was influenced by the ingestion of different types of fat containing benzo(a)pyrene [B(a)P], a prototypical PAH compound. Treatment consisted of 25 and 50 μg B(a)P/kg body wt., dissolved in tricaprylin, administered to 7-week-old male PIRC rat daily via oral gavage for 60 days. One group of rats received the AIN-76A control diet and the other group, the Western diet throughout the duration of this study. At the end of exposure, rats were sacrificed; colons were retrieved and preserved in 10% formalin for observation of gross pathological changes. An increased prevalence of adenomas in colon of rats that were maintained on Western diet compared to AIN-76A diet and controls (P < 0.05) was noticed. Interestingly, we have also observed adenomas with high grade dysplasia in B(a)P + Western diet group and these incidences were of frequent occurrence at 50 μg/kg compared to 25 μg/kg B(a)P dose group. On the other hand, the B(a)P alone, and AIN-76A diet groups did not show significant differences in the numbers of adenomas and invasive tumors in colon. Also, B(a)P treatment-related changes were seen in body weight and food consumption of rats administered with B(a)P, with the changes more pronounced in the body weight gain of Western diet group compared to the AIN-76A diet group and controls (p < 0.005). In summary, our studies established that Western diet potentiates the development of colon tumors caused by B(a)P in the PIRC rat. Citation Format: Kelly L. Harris, Mohammad S. Niaz, Awadh A. Binhazim, Mary K. Washington, Samuel E. Adunyah, Aramandla Ramesh. Obesity enhances benzo(a)pyrene-induced colon tumorigenesis in a PIRC rat model of colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1278. doi:10.1158/1538-7445.AM2013-1278