Browse > Article
http://dx.doi.org/10.5487/TR.2018.34.3.259

Genotoxicity Study of Glycopeptide (G-7%NANA)  

Kim, Ha-Young (GLP center and Department of Toxicity Assessment, Daegu Catholic University)
Kim, Min-Hee (GLP center and Department of Toxicity Assessment, Daegu Catholic University)
Kim, Hee-Kyong (Hanilbiomed Co.)
Park, Yeong-Chul (GLP center and Department of Toxicity Assessment, Daegu Catholic University)
Publication Information
Toxicological Research / v.34, no.3, 2018 , pp. 259-266 More about this Journal
Abstract
Glycomacropeptide (GMP), a whey protein of milk, has functions including differentiation and development of nervous system, and anticancer and antiviral effects. To develop new functions, N-acetylneuraminic acid (NANA) containing 7% sialic acid was separated from GMP to produce G-7%NANA. N-glycolylneuraminic acid (Neu5Gc) is another type of sialic acid separated from GMP, which has been linked to immune disorders and chronic inflammation-mediated diseases. Therefore, safety was a concern in the use of G-7%NANA in functional foods. To ensure safety, in this study, three genetic toxicity tests on G-7%NANA were conducted. In the reverse mutation test using Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA, and in the chromosome aberration test using CHO-K1 cells, no significant differences from negative control were found at all dose levels. Similarly, no dose-related differences were evident compared to negative control in the micronucleus test using ICR mice. There was no evidence of G-7%NANA-related genetic toxicity.
Keywords
Glycomacropeptide; N-acetylneuraminic acid; Genetic toxicity test; Sialic acid; N-acetylneuraminic acid;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Swaisgood, H. (1974) Primary sequence of kappa-casein. J. Dairy Sci., 58, 583-592.
2 Manso, M.A. and Lopez-Fandino, R. (2004) ${\kappa}$-Casein macropeptide from cheese whey: Physicochemical, biological, nutritional, and technological features for possible uses. Food Rev. Int., 20, 329-355.   DOI
3 Nesser, J.R. (1991) Anti-plaque and anticaries agent. United States Patent 4994441.
4 Moon, Y.I., Lee, W.J. and Oh, S.J. (2005) Glycomacropeptide hydrolysed from bovine ${\kappa}$-casein; II. Chromatographic changes of ${\kappa}$-casein macropetide as related to trichloroacetic acid concentration. Korean J. Food Sci. Anim. Resour., 25, 478-482.
5 Wang, B. and Brand-Miller, J. (2003) The role and potential of silaic acid in human nutrition. Eur. J. Clin. Nutr., 57, 1351-1369.   DOI
6 Allen, A. (1984) Sialic Acids: Chemistry, Metabolism and Function (Schauer, S. Ed.). Springer-Verlag, Wien and New York, pp. 75.
7 Wang, B., Brand-Miller, J., McVeagh, P. and Petocz, P. (2001) Concentration and distribution of sialic acid in human milk and infant formulas. Am. J. Clin. Nutr., 74, 510-515.   DOI
8 Schauer, R., Kelm, S., Reuter, G. and Roggentin, P. (1995) Biochemistry and role of sialic acid in Biology of the Sialic Acids (Rosenberg, A. Ed.). Plenum Press, New York, pp. 7-49.
9 Schauer, R. and Kamerling, J.P. (1997) Chemistry, biochemistry and biology of sialic acids in Glycoproteins II (Schachter, J., Montreuil, J. and Vliegenthart, J.F.G. Eds.). Elsevier, Amsterdam, pp. 243-372.
10 Urashima, T., Saito, T., Nakamura, T. and Messer, M. (2001) Oligosaccharides of milk and colostrum in non-human mammals. Glycoconj. J., 18, 357-371.   DOI
11 Newburg, D.S. and Neubauer, S.H. (1995) Carbohydrates in milks: Analysis, quantities, and significance in Handbook of Milk Composition (Jensen, R.G. Ed.). Academic Press, San Diego, pp. 273-338.
12 Warren, L. (1994) Bound Carbohydrates in Nature, Cambridge University Press, New York
13 Nesser, J.R. (1991) Anti-plaque and anticaries agent. United States Patent 4992420.
14 Schupbach, P., Neeser, J.R., Golliard, M., Rouvet, M. and Guggenheim, B. (1996) Incorporation of caseinoglycomacropeptide and caseinophosphopeptide into the salivary pellicle inhibits adherence of mutant streptococci. J. Dent. Res., 75, 1779-1788.   DOI
15 Aimutis, W.R. (2004) Bioactive properties of milk proteins with particular focus on acticariogenesis. J. Nutr., 134, 989-995.   DOI
16 Dosako, S., Kusano, H., Deya, E. and Idota, T. (1992) Infection protectant. United States Patent 5147853.
17 Kawasaki, Y., Isoda, H., Shinmoto, H., Tanimoto, M., Dosako, S., Idota, T. and Nakajima, I. (1993) Inhibition by ${\kappa}$-casein glycomacropeptide and lactoferrin of influenza virus hemagglutination. Biosci., Biotechnol., Biochem., 57, 1214-1215.
18 Yvon, M., Beucher, S., Guilloteau, P., Huerou-Luron, I.L. and Corring, T. (1994) Effects of caseinomacropeptide (CMP) on digestion regulation. Reprod. Nutr. Dev., 34, 527-537.   DOI
19 Corring, T., Beaufrere, B. and Maubois, J.L. (1997) Release of cholecystokinin in humans after ingestion of glycomacropeptide (GMP) in The 1997 International Whey Conference. Rosemount, IL.
20 JEMS-MMS (1998) Atlas of Chromosome Aberration by Chemicals. Jap. Environ. Mutagen Soc-Mamm, Mutagenicity Study Group, Tokyo.
21 Tangvoranuntakul, P., Gagneux, P., Diaz, S., Varki, N., Muchmore E. and Varki, A. (2000) Expression of N-glycolyl-neuraminic acid in normal, fetal and malignant human tissues. Glycobiology, 10, 53 (Abstract).
22 Wang, B. (2009) Sialic acid is an essential nutrient for brain development and cognition. Annu. Rev. Nutr., 29, 177-222.   DOI
23 Amon, R., Reuven, E.M., Ben-Arye, S.L. and Padler-Karavani, V. (2014) Glycans in immune recognition and response. Carbohydr. Res., 389, 115-122.   DOI
24 Shamberger, R.J. (1984) Serum sialic acid in normals and in cancer patients. J. Clin. Chem. Clin. Biochem., 22, 647-651.
25 Pearce, O.M. and Laubli, H. (2016) Sialic acids in cancer biology and immunity. Glycobiology, 26, 111-128.   DOI
26 Greenwood, S.K., Hill, R.B., Sun, J.T., Armstrong, M.J., Johnson, T.E., Gara, J.P. and Galloway, S.M. (2004) Population doubling: a simple and more accurate estimation of cell growth suppression in the in vitro assay for chromosomal aberrations that reduces irrelevant positive results. Environ. Mol. Mutagen., 43, 36-44.   DOI
27 Ishidate, M., Jr. (1987) Data Book of Chromosomal Aberration Test in vitro (Revised edition), Life-Science Information Center, Tokyo, pp. 31-46.
28 Alais, C. and Jolles, P. (1961) Etude comparee des caseino-glycopeptides formes par action de la presure sur les caseines de vache, de brebis et de chevre: II. Etude de la partie nonpeptidique. Biochim. Biophys. Acta, 51, 315-322.   DOI
29 Schauer, R. (1982) Sialic Acids, Chemistry, Metabolism, and Function, Springer-Verlag, New York.
30 Abad-Rodriguez, J. and Robotti, A. (2007) Regulation of axonal development by plasma membrane gangliosides. J. Neurochem., 103, 47-55.   DOI
31 Nielsen, P. and Tromholt, N. (1994) Method for production of kappa-casein glycomacropeptide and use of a kappa-casein glycomacropeptide. World Patent WO 9415952.
32 Carlson, S.E., Werkman, S.H. and Tolley, E.A. (1996) Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. Am. J. Clin. Nutr., 63, 687-697.   DOI
33 Gibson, R.A. (1999) Long-chain polyunsaturated fatty acids and infant development. Lancet., 354, 1919-1920.   DOI
34 Yogeeswaran, G. and Salk, P.L. (1981) Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines. Science, 212, 1514-1516.   DOI
35 Ishikawa, M. and Koizumi, S. (2010) Microbial production of N-acetylneuraminic acid by genetically engineered Escherichia coli. Carbohydr. Res., 345, 2605-2609.   DOI
36 Zimmermann, V., Hennemann, H.G., Daussmann, T. and Kragl, U. (2007) Modelling the reaction course of N-acetyl-neuraminic acid synthesis from N-acetyl-D-glucosamine new strategies for the optimisation of neuraminic acid synthesis. Appl. Microbiol. Biotechnol., 76, 597-605.   DOI
37 Maron, D.M. and Ames, B.N. (1983) Revised methods for the Salmonella mutagenicity test. Mutat. Res., 173-215.
38 Park, Y.C., Kim, M.H., Kim, J.W., Kim, J.B., Lee, J.G., Yu, C.Y., Kim, S.H., Chung, I.M., Kim, J.K., Choi, R.N. and Lim, J.K. (2014) Genotoxicity study of polysaccharide fraction from Astragalus membranaceus's aerial parts. Toxicol. Res., 30, 131-138.   DOI