Abstract B34: Association of endogenous oxidative and aldehyde stress: Implications for studies of colon carcinogenesis

The results of a small pilot study provided new insights into the process of colon carcinogenesis. Background: The known risk factors for colorectal cancer (CRC) suggested that CRC resulted from the interaction of exposure to energy excess and to oxidative stress [McKeown-Eyssen G et al. pp 673-693 in “Endogenous Toxins” Wiley, 2010]. The suggestion was supported by: cellular studies that demonstrated the cytotoxicity and genotoxicity of excess energy substrate (fructose) with oxidative stress (H 2 O 2 ); animal studies that showed a wide range of pathology associated with fructose-based diets when combined with oxidative stress; and clinical studies that described the association of advanced glycation end-products (AGEs) with chronic diseases associated with the Western lifestyle. Methods: A pilot case-control study at a hospital-based gastroenterology clinic was conducted to assess methods for future tests of the hypothesis. It was based on an analysis of plasma samples collected from patients with (n = 20) or without (n = 21) colonoscopy-demonstrated polyps. Results: Although as anticipated none of the differences between polyp and non-polyp plasma samples achieved statistical significance, there were unexpectedly strong associations of the concentrations of the endogenous plasma aldehydes, glyoxal and methylglyoxal (r = 0.92), and glyoxal and 4-hydroxynonenal (r = 0.52) across the collected samples. Conclusions: The associations were likely a consequence of the known interaction of endogenous aldehydes with oxidative stress: endogenous aldehydes increased oxidative stress; oxidative stress increased the formation of endogenous aldehydes [e.g. Vander Jagt DL. Drug Metab Drug Interact 2008;23:93-124]. The products of such interactions, AGEs and advanced lipid oxidation endproducts (ALEs), could explain the known accumulation of fluorescent lipofuscin observed with dysplastic adenomas. Impact: Exposure to endogenous aldehydes and oxidation products is complex. Endogenous aldehyde derived — AGEs could provide robust biomarkers of this exposure including information relating to the tissues, cells and cellular organelles affected. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B34.