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.
Highlights
Colorectal cancer (CRC) is one of the most common cancers in the Western world
Some changes in body weight and food consumption were noticed, these changes were observed within each treatment group over the 60 day exposure. These results prompted us to investigate if diet type and B(a)P dose had an influence on adipose tissue mass accrued in the body of the polyposis in rat colon (PIRC) rats
The B(a)P doses employed in our study are relevant to human exposure scenarios as the levels of polycyclic aromatic hydrocarbons (PAHs) are similar to levels that would be acquired in the diet
Summary
Colorectal cancer (CRC) is one of the most common cancers in the Western world. In the United States alone, nearly 136,830 new cases of CRC have been diagnosed, and 50,310 deaths will occur due to this cancer this year alone [1]. Epidemiological studies have shown that environmental factors, and especially diet, play an important role in susceptibility to sporadic colon cancer [2] These studies estimate that diet contributes to up to 80% of documented colorectal cancer (CRC) cases. With at least 20 PAHs detectable in most dietary items [5], it is no surprise that they have been reported to have an impact on obesity due to their highly lipophilic nature and presence in foods that are high in saturated fats [6] This necessitates using a prototypical PAH compound such as benzo(a)pyrene [B(a)P] to www.impactjournals.com/oncotarget understand the mechanisms involved in development of colorectal cancer by PAHs. In exposed individuals, B(a)P is metabolized by cytochrome P450 into metabolites, many of which are highly reactive and can form to DNAadducts [7], predisposing the individual to cancer
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