Sporadic colon cancers have been shown to be triggered by diet and environmental factors. Epidemiological studies have shown that colon cancer rates were significantly reduced in Mediterranean countries where olive oil is the main ingredient of diet. Published works have shown that olive oil inhibits cell proliferation and promotes apoptosis in colorectal cancer cell lines. Studies conducted earlier in our laboratory have shown that dietary exposure to the environmental toxicant benzo(a)pyrene (BaP) leads to colon tumor formation. Benzo(a)pyrene biotransformation studies have shown that once BaP is metabolized by cytochrome P450 drug metabolizing enzymes, it forms metabolites such as BaP 7, 8-diol-epoxide (BPDE), BaP 3,6 & 6,12-diones. These metabolites have also been shown to cause double stranded breaks in DNA and cause oxidative damage. Therefore, we hypothesize that olive oil's interaction with BaP will modulate BaP metabolism and reduce colon tumor formation. In this study we investigated the effect of olive oil on BaP-induced colon carcinogenesis in male ApcMin mice. Mice were assigned to a control (n=7) or treatment group (n =7). Treatment consisted of 50 and 100 μg BaP/kg body weight dissolved in tricaprylin (BaP-only group) or olive oil administered daily via oral gavage for sixty days. Post exposure, mice were sacrificed; colon and liver tissues were retrieved from each group of mice and were preserved in formalin and pathological changes were evaluated. The tissues were further analyzed for the induction of drug metabolizing enzymes such as cytochrome 1A, cytochrome 1B1, and glutathione S-Transferase. Additionally, to determine if BaP caused oxidative DNA damage to tissues, genomic DNA was isolated from the respective tissues and we quantified aldehyde lesions. There was a reduced incidence of adenomas in colons of mice that ingested BaP + olive oil compared to mice that received BaP only (p < 0.05). CYP protein expression was reduced while GST protein expression increased in the colon and liver tissues of BaP + olive oil-treated mice compared to BaP only-treated mice. The BaP organic metabolite concentrations decreased, while aqueous metabolite concentrations increased in the BaP + olive oil group compared to BaP only-treatment group. DNA lesions were increased in the colon and liver tissues of BaP-treated mice compared to BaP + olive oil treated mice. In summary, our studies suggest that olive oil exerts a protective effect against BaP-induced colon cancer.
Citation Format: Leah D. Banks, Priscilla Amoah, Mohammad S. Niaz, Mary K. Washington, Samuel E. Adunyah, Aramandla Ramesh. Olive oil alters benzo(a)pyrene biotransformation and reduces oxidative DNA damage in colon of ApcMin mouse. [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 1589. doi:10.1158/1538-7445.AM2014-1589