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
Abstract
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.
Footnotes
-
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The work of E. E. was supported by Deutsche Krebshilfe e.V. (German Cancer Aid). W. S. Scheppach received Grant Sche 252/2-1 from the Deutsche Forschungsgemeinschaft.
-
↵2 To whom requests for reprints may be addressed, at Department of Toxicology, University of Wuerzburg, Versbacher Strasse 9, D-97078 Wuerzburg, Germany. E-mail: eder{at}toxi.uni-wuerzburg.de
-
↵3 To whom requests for reprints may be addressed, at Department of Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany. E-mail: w.scheppach{at}medizin.uni-wuerzburg.de
-
↵4 The abbreviations used are: RS, resistant starch; LI, labeling index; BrdUrd, bromodeoxyuridine; HNE, trans-4-hydroxy-2-nonenal; dGp,; MDA, malondialdehyde; BME, Eagle’s medium with Earle’s salts, FCS, and antibiotic-antimycotic solution; NP1, nuclease P1; dGp = deoxyguanosine-3′-monophosphate.
-
- Accepted May 23, 1902.
- Received July 6, 1901.
- Revision received May 16, 1902.
