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Effect of Enzyme-resistant Starch on Formation of 1,N²-Propanodeoxyguanosine Adducts of trans-4-Hydroxy-2-nonenal and Cell Proliferation in the Colonic Mucosa of Healthy Volunteers¹

Departments of Toxicology [M. W., P. W., E. E.] and Medicine [S. H., A. G., W. S.], University of Wuerzburg, D-97078 Wuerzburg, Germany

The effect of enzyme-resistant starch (RS) on the development of colon cancer was reported to include both chemopreventive activity in humans and tumorigenic activity in animals. A study was performed to detect the influence of enzyme-RS on lipid peroxidation-induced DNA damage and cell proliferation. During two 4-week periods, 12 volunteers consumed a controlled diet in which starchy foods were enriched with a highly resistant amylomaize starch (Hylon VII) in the high-RS period and with an available corn starch in the low-RS period (second period). At the end of each test period, biopsy specimens of the rectosigmoidal mucosa were obtained from each subject and analyzed for trans-4-hydroxy-2-nonenal-1,N²-propanodeoxyguanosine-3'-monophosphate adducts using a ³²P postlabeling assay, and cell proliferation was determined by bromodeoxyuridine labeling. The trans-4-hydroxy-2-nonenal-1,N²-propanodeoxyguanosine-3'-monophosphate adduct level of DNA from colonic mucosa of eight evaluated volunteers was significantly higher in the high-RS period (mean adducts/10⁷ nucleotides ± SD, 3.83 ± 0.60) than in the low-RS period (2.69 ± 0.35; P < 0.05). There was no evidence for an increased cell proliferation in the upper crypt in the high-RS phase, compared with the low-RS phase. There are indications now that enzyme-RS induces oxidative stress that is not correlated with increased cell proliferation. If it is accepted that the formation of DNA adducts reflects oxidative stress, which in turn accelerates the process of carcinogenesis, then certain forms of RS may have a tumor-enhancing effect rather than a tumor-protective effect.

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