5. tissue samples were analyzed by reverse phase high-performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the32P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose-dependent manner, with 100 g/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater Mogroside VI concentration of B(a)P metabolites, compared to the 50 g/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen. Keywords:Benzo(a)pyrene, Polycyclic aromatic hydrocarbons, ApcMinmouse, Colon cancer, Biotransformation, Metabolites, B(a)P-DNA adducts == 1. Introduction == Colorectal cancer (CRC) is one of the most common cancers in the Western world. In the United States alone, nearly 143, 460 new cases of CRC have been diagnosed recently and 51,690 will die of this cancer [1]. People get colon cancer through hereditary (familial) and sporadic means. Sporadic gene mutation seems to play an important role in the development of tumors in 90% of the colon cancer cases in which there is no familial history of colon cancer [2]. Dietary factors and environmental agents have been suspected of causing sporadic gene mutations and therefore involved in the induction of sporadic colon carcinomas [3]. Global cancer statistics reveal that this cancer is a major cause of cancer deaths in the western world [4]. Specific components of western diet including consumption of meat (particularly red and/or well-done meat) and dietary fat (particularly polyunsaturated and saturated fatty acids) have been proposed as risk factors that influence susceptibility to colorectal cancer [5,6]. An overwhelming epidemiological evidence indicates that red meat intake and excessive adiposity increase susceptibility to colorectal neoplasia [79]. Of the several environmental chemicals reported to contribute to toxicity of the gastrointestinal system, the polycyclic aromatic hydrocarbons (PAHs) have garnered a CalDAG-GEFII lot of interest as they are formed in barbecued meat [1012]. In addition to their formation during cooking, PAHs are also emanated from environmental [13, 14] and occupational [15,16] sources, thus contributing significantly to dietary contamination, intake and development of CRC in humans [17,18]. The concentrations of PAHs found in products of plant and animal origin have extensively been reviewed and the intake ranged from 0.02 to 3.6 g per person per day [10]. Grilled and barbecued meats were reported to contain high levels of benzo(a)pyrene [B(a)P; a prototypical PAH compound] compared to pan-fried and boiled foods Mogroside VI [19] and contributes to 21% of mean daily intake of B(a)P [20]. Epidemiological studies provide evidence for a consistent interaction between PAH-associated fatty diet/red meat intake and CRC development. Findings from a clinic-based casecontrol study bolster the hypothesis that dietary intake of PAHs is associated with CRC risk [21]. Using the same study design and a sample size of about 4000 adenoma cases, this research group [22,23] also showed that consumption of well-done red meat was associated with increased risks for colon adenomas. Similar to the above-mentioned studies, another sigmoidoscopy- based study (275 CRC cases) reported an association among high intake of barbecued red meat, B(a)P, and colorectal adenomas [24]. In a colonoscopy study that involved more than 2500 subjects, a statistically significant doseresponse relationship between adenoma incidence in colon and dietary exposure to B(a)P was revealed [6]. In Mogroside VI another study involving 370 cases of CRC, high intake of B(a)P was associated with an increased risk of CRC among individuals carrying the CT genotype forUGT1A(UDP-glucuronosyltransferase1A), a phase II enzyme involved in the detoxification of B(a)P. Additionally, correlation between total mutagenic activity and adenomas was found to be high for B(a)P [25]. A recent study that comprised of 1008 subjects revealed an elevated risk of rectal adenoma (early neoplasia) in association with B(a)P intake through meat [26]..