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Nucleosides and nucleotides: natural bioactive substances in milk and colostrum

Published online by Cambridge University Press:  09 March 2007

Eckhard Schlimme*
Affiliation:
Bundesanstalt für Milchforschung, Institut für Chemie und Physik, Kiel, Germany
D. Martin
Affiliation:
Bundesanstalt für Milchforschung, Institut für Chemie und Physik, Kiel, Germany
H. Meisel
Affiliation:
Bundesanstalt für Milchforschung, Institut für Chemie und Physik, Kiel, Germany
*
*Corresponding author: Professor E. Schlimme, fax +49 431 609-2300, email [email protected]
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Abstract

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Nucleotides, nucleosides and nucleobases belong to the non-protein-nitrogen (NPN) fraction of milk. The largest amounts of ribonucleosides and ribonucleotides – ribose forms only were considered in this review – were measured directly after parturition in bovine milk and other ruminants as well as in the milk of humans. Generally, concentrations of most of the nucleos(t)ides tend to decrease gradually with advancing lactation period or nursing time. The species-specific pattern of these minor constituents in milk from different mammals is a remarkable property and confirms, at least, the specific physiological impact of these minor compounds in early life. The physiological capacity of these compounds in milk is given by the total potentially available nucleosides. The main dietary sources of nucleos(t)ides are nucleoproteins and nucleic acids which are converted in the course of intestinal digestion into nucleosides and nucleobases the preferred forms for absorption in the intestine. Thus, nucleosides and nucleobases are suggested to be the acting components of dietary and/or supplemented nucleic acid-related compounds in the gut. They are used by the body as exogenous trophochemical sources and can be important for optimal metabolic functions. Up to 15 % of the total daily need for a breast-fed infant was calculated to come from this dietary source. Concerning their biological role they not only act as metabolites but are also involved as bioactive substances in the regulation of body functions. Dietary nucleotides affect immune modulation, e.g. they enhance antibody responses of infants as shown by a study with more than 300 full-term healthy infants. Dietary nucleos(t)ides are found to contribute to iron absorption in the gut and to influence desaturation and elongation rates in fatty acid synthesis, in particular long-chain polyunsaturated fatty acids in early stages of life. The in vitro modulation of cell proliferation and apoptosis has been described by ribonucleosides, in particular by modified components using human cell culture models. Due to the bio- and trophochemical properties of dietary nucleos(t)ides, the European Commission has allowed the use of supplementation with specific ribonucleotides in the manufacture of infant and follow-on formula. From the technochemical point of view, the ribonucleoside pattern is influenced by thermal treatment of milk. In addition ribonucleosides are useful indicators for quantifying adulterations of milk and milk products.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2000

References

Aronow, B, Toll, D, Patrick, J, Hollingsworth, P, McCartan, K & Ullman, B (1986) Expression of a novel high-affinity purine nucleobase transport function in mutant mammalian T-lymphoblasts. Molecular and Cellular Biology 6, 29572962.Google ScholarPubMed
Barness, LA & Carver, JD (1996) Nucleotides and the neonatal immune response. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 191194 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Belt, JA & Noel, LD (1988) Isolation and characterization of a mutant of L1210 murine leukemia deficient in nitrobenzylthioinosine – insensitive nucleoside transport. Journal of Biological Chemistry 263, 1381913822.CrossRefGoogle ScholarPubMed
Borek, E (1971) tRNA and tRNA modification in differentiation and neoplasia. Cancer Research 31, 596597.Google ScholarPubMed
Bronk, JR & Hastewell, JG (1987) The transport of pyrimidines into tissue rings cut from rat small intestine. Journal of Physiology (London) 382, 475488.CrossRefGoogle ScholarPubMed
Carlson, SE, Rhodes, PG & Fergusson, MG (1986) Docosahexaenoic acid status of preterm infants at birth and following feeding with human or milk formula. American Journal of Clinical Nutrition 44, 789804.CrossRefGoogle ScholarPubMed
Carlson, SE, Rhodes, PG, Rao, VS & Goldgar, DE (1987) Effect of fish oil supplementation on the n-3 fatty acid content of red blood cell membranes in preterm infants. Pediatric Research 21, 507510.CrossRefGoogle ScholarPubMed
Carver, JD, Cox, WI & Barness, LA (1990) Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation. Journal of Parenteral and Enteral Nutrition 14, 1822.CrossRefGoogle ScholarPubMed
Commission Directive (1996) 96/4/EC of 16 February 1996 amending Directive 91/321/EEC on infant formulae and follow-on formulae Official Journal of the European Communities No L49, 1216.Google Scholar
Darnowski, JW, Holdridge, C & Handschumacher, RE (1987) Concentrative uridine transport by murine spleenocytes: kinetics, substrate specificity and sodium dependency. Cancer Research 47, 26142619.Google Scholar
DeLucchi, C, Pita, ML, Faus, MJ, Molina, JA, Uauy, R & Gil, A (1987) Effects of dietary nucleotides on the fatty acid composition of erythrocyte membrane lipids in term infants. Journal of Pediatric Gastroenterology and Nutrition 6, 568574.Google ScholarPubMed
Deutsch, A & Nilsson, R (1960) Über die säurelöslichen Nucleotide der Frauenmilch. Hoppe-Seylers Zeitschrift Physiologische Chemie 321, 246251.CrossRefGoogle Scholar
Faelli, A & Esposito, G (1970) Effect of inosine and its metabolites on intestinal iron absorption in the rat. Biochemical Pharmacology 19, 25512554.CrossRefGoogle ScholarPubMed
Fairbairn, HA & Litt, MA (1922) Nuclein in the treatment of pneumonia and other infections. Medical Times 8, 205206.Google Scholar
Gehrke, CW & Kuo, KCT (1990) Chromatographie and modification of nucleosides; part C: modified nucleosides in cancer and normal metabolism. In Journal of Chromatography Library, Vol. 45C, Amsterdam: Elsevier Publishers.Google Scholar
Gil, A, Lozano, E, DeLucchi, C, Maldonado, J, Molina, JA & Pita, M (1988) Changes in the fatty acid profiles of plasma lipid fractions induced by dietary nucleotides in infants born at term. European Journal of Clinical Nutrition 42, 473481.Google Scholar
Gil, A, Pita, M, Martinez, A, Molina, JA &, Sanchez-Medina, F (1986) Effect of dietary nucleotides on the plasma fatty acids in at-term neonates. Human Nutrition Clinical Nutrition 40, 185195.Google ScholarPubMed
Gil, A &, Sanchez-Medina, F (1981 a) Acid-soluble nucleotides of cow's, goat's and sheep's milks at different stages of lactation. Journal of Dairy Research 48, 3544.CrossRefGoogle ScholarPubMed
Gil, A &, Sanchez-Medina, F (1981 b) The determination of acid-soluble nucleotides in milk by improved enzymatic methods: A comparison with the ion-exchange column chromatography procedure. Journal of the Science of Food and Agriculture 32, 11231131.Google Scholar
Gil, A &, Sanchez-Medina, F (1982) Acid-soluble nucleotides of human milk at different stages of lactation. Journal of Dairy Research 49, 301307.CrossRefGoogle ScholarPubMed
Griffith, DA & Jarvis, SM (1993) High-affinity sodium-dependent nucleobase transport in cultured renal epithelial cells (LLC-PK1). Journal of Biological Chemistry 268, 2008520090.CrossRefGoogle ScholarPubMed
Groß, H, Topp, H, Heller-Schöch, G &, Schöch, G (1992) Modifizierte Ribonucleoside in Frauenmilch. Ernährungsumschau 39, 21.Google Scholar
Gutiérrez, MM, Brett, CM, Ott, RJ, Hui, AC & Giacomini, KM (1992) Nucleoside transport in brush-border membrane vesicles from human kidney. Biochimica et Biophysica Acta 1105, 19.CrossRefGoogle ScholarPubMed
Gyorgy, P (1971) Biochemical aspects of human milk. American Journal of Clinical Nutrition 24, 970975.CrossRefGoogle ScholarPubMed
Hickman, JA (1992) Apoptosis induced by anticancer drugs. Cancer Metastasis Review 11, 121139.CrossRefGoogle ScholarPubMed
Janas, LM & Picciano, MF (1982) The nucleotide profile of human milk. Pediatric Research 16, 659662.CrossRefGoogle ScholarPubMed
Jarvis, SM (1989) Characterization of sodium-dependent nucleoside transport in rabbit intestinal brush-border membrane vesicles. Biochimica et Biophysica Acta 979, 132138.CrossRefGoogle ScholarPubMed
Jarvis, SM (1996) Nucleoside and nucleobase transport in animal cells. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 87110 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Johke, T & Goto, T (1962) Acid-soluble nucleotides in cow's and goat's milk. Journal of Dairy Science 45, 735741.CrossRefGoogle Scholar
Kobata, A (1963) The acid-soluble nucleotides of milk. II. Isolation and identification of two novel uridine nucleotide oligosaccharide conjugates from human milk and colostrum. Journal of Biochemistry 53, 167175.CrossRefGoogle ScholarPubMed
Koletzko, B, Schmidt, E, Bremer, HJ, Haug, M & Harzer, G (1989) Effect of dietary long-chain polymers saturated fatty acids on the essential fatty acid status of premature infants. European Journal of Pediatrics 148, 669675.CrossRefGoogle Scholar
Larson, BL (1976) Comparative production of β-lactoglobulin and orotic acid with lactose in bovine mammary cell cultures: effects of cell density and constituent inhibition. Journal of Dairy Science 59, 18811889.CrossRefGoogle ScholarPubMed
Larson, BL, Heary, HL Jr & Devery, JE (1980) Immunoglobulin production and transport by the mammary gland. Journal of Dairy Science 63, 665671.CrossRefGoogle ScholarPubMed
Le Hir, M & Dubach, UC (1985) Concentrative transport of purine nucleosides in Grush-border vesicles of rat kidney. European Journal of Clinical Investigation 15, 121127.CrossRefGoogle ScholarPubMed
Leach, JL, Baxter, JH, Molitor, BE, Ramstack, MB & Masor, ML (1995) Total potentially available nucleosides of human milk by stage of lactation. American Journal of Clinical Nutrition 61, 12241230.CrossRefGoogle ScholarPubMed
Lee, CW, Cheeseman, CI & Jarvis, SM (1988) Na+- and K+-dependent uridine transport in rat renal brush-border membrane vesicles. Biochimica et Biophysica Acta 942, 139149.CrossRefGoogle ScholarPubMed
Leist, M & Nicotera, P (1997) Breakthroughs and views. The shape of cell death. Biochemical and Biophysical Research Communications 236, 19.CrossRefGoogle Scholar
Leleiko, NS, Bronstein, AD, Baliga, BS & Munro, HN (1983) De novo purine nucleotide synthesis in the rat small and large intestines. Effect of dietary protein and purines. Journal of Pediatric Gastroenterology and Nutrition 2, 313319.CrossRefGoogle ScholarPubMed
Leleiko, NS, Bronstein, AD & Munro, HN (1979) Effect of dietary purines on de novo synthesis of purine nucleotides in the small intestinal mucosa. Pediatric Research 13, 403.Google Scholar
Leleiko, NL, Martin, BA, Walsh, M, Kazlow, P, Rabinowitz, S & Sterling, K (1987) Tissue-specific gene expression results from a purine- and pyrimidine-free diet and 6-mercaptopurine in the rat small intestine and colon. Gastroenterology 93, 10141020.CrossRefGoogle ScholarPubMed
Manson, W (1956) Acid-soluble nucleotides of lactating mammary gland. Biochimica et Biophysica Acta 19, 398399.CrossRefGoogle ScholarPubMed
Martin, SJ, Green, DR & Cotter, TG (1994) Dicing with death: dissecting the components of the apoptosis machinery. Trends Biochemical Science 19, 2630.CrossRefGoogle ScholarPubMed
Martin, D, Kiesner, C, Lorenzen, PChr & Schlimme, E (1998) Adenosin-Desaminase (EC 3.5.4.4): Ein potentieller Hitzeindikator zur Unterscheidung von kurzzeit- und hocherhitzter Konsummilch. Kieler Milchwirtschaftliche Forschungsberichte 50, 225233.Google Scholar
Martin, D, Kiesner, C & Schlimme, E (1995) Kinetische Analyse der Dimroth-Umlagerung des 1-Methyladenosins in Milch unter Temperatur-Zeit-Bedingungen des Sterilbereichs. Kieler Milchwirtschaftliche Forschungsberichte 47, 7586.Google Scholar
Martin, D, Kiesner, C & Schlimme, E (1997) Ribonucleosides: chemical parameters for controlling the heat treatment of milk. Nahrung/Food 41(5), 258267.CrossRefGoogle Scholar
McMillan, JA, Oski, FA, Lourie, G, Tomarelli, RM & Landau, SA (1977) Iron absorption from human milk, simulated human milk, and proprietary formulas. Pediatrics 60, 896900.CrossRefGoogle ScholarPubMed
Meisel, H, Günther, S, Martin, D & Schlimme, E (1998) Apoptosis induced by modified ribonucleosides in human cell culture systems. FEBS Letters 433, 265268.CrossRefGoogle ScholarPubMed
Meisel, H, Hartmann, R, Martin, D & Schlimme, E (1999) Modulating effects of adenosine and modified adenine nucleosides on human cells (HL-60). Nahrung/Food 43, 213215.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Meisel, H, Lorenzen, PChr, Martin, D & Schlimme, E (1997) Chemometric differentiation of butter types by analysis of compositional parameters with neural networks. Nahrung/Food 41, 7580.CrossRefGoogle Scholar
Molina, JA, Romera, JM, Gil, A, AGil, and RUauy (1996) Nucleotides and nucleic acids in human milk. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 6367 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Ohyanogi, H, Nishimatsu, S, Nomura, H, Kawamura, M, AGil, and RUauy (1996) Effect of nucleotides and nucleosides on cell growth in vitro and in vivo. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 145168 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Ott, FG & Schlimme, E (1991) Thermisch induzierte Bildung von N6-Methyladenosin in Milch. Kieler Milchwirtschaftliche Forschungsberichte 43, 213217.Google Scholar
Pickering, LK, Granoff, DM, Erickson, JR, Masor, ML, Cordle, LT, Schaller, JP, Winship, TR, Paule, CL & Hilty, MD (1998) Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 101, 242249.CrossRefGoogle ScholarPubMed
Pita, ML, Fernandez, MR, De-Lucchi, C, Medina, A, Martinez-Valverde, A, Uauy, R & Gil, A (1988) Changes in the fatty acids pattern of red blood cell phospholipids induced by type of milk, dietary nucleotide supplementation, and postnatal age in preterm infants. Journal of Pediatric Gastroenterology and Nutrition 7, 740747.Google ScholarPubMed
Plagemann, PGW & Wohlheuter, RM (1984) Hypoxanthine transport in mammalian cells: cell type-specific differences in sensitivity to inhibition by dipyridamole and uridine. Journal of Membrane Biology 81, 255262.CrossRefGoogle ScholarPubMed
Putnam, JC, Carlson, SE, DeVoe, PW & Barness, LA (1982) The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. American Journal of Clinical Nutrition 36, 106114.CrossRefGoogle ScholarPubMed
Raezke, K-P, Frister, H, Pabst, K & Schlimme, E (1988) Ribonucleoside als minore Milchinhaltsstoffe. II. Untersuchung des Ribonucleosidmusters in Rohmilch während der zweiten Hälfte der Lactationsphase. Milchwissenschaft 43, 294298.Google Scholar
Raezke, K-P & Schlimme, E (1990) Ribonucleoside in Milch: Charakterisierung und Bestimmung des Konzentrationsprofils dieser minoren Komponenten über eine Laktationsperiode. Zeitschrift für Naturforschung 45, 655662.CrossRefGoogle Scholar
Robertson, LE, Chubb, S, Meyn, RE, Story, M, Ford, R, Hittelman, WN & Plunkett, W (1993) Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2′deoxyadenosine and 9-β-D-arabinosyl-2-fluoroadenine. Blood 81, 143150.CrossRefGoogle ScholarPubMed
Sanchez-Medina, F & Gil, A (1996) Dietary nucleotides and polyunsaturated fatty acid metabolism. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 111120 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Sanchez-Pozo, A, Gil, A, AGil, and RUauy (1996) Influence of dietary nucleotides on neonatal lipoprotein metabolism. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 133144 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Sanchez-Pozo, A, Pita, ML, Martinez, A, Molina, JA, Sanchez-Medina, F & Gil, A (1986) Effects of dietary nucleotides upon lipoprotein pattern of newborn infants. Nutrition Research 6, 763771.CrossRefGoogle Scholar
Schlimme, E, Boos, K-S, CWGehrke, and KCKuo (1990) Ribonucleosides in body fluids – on-line chromatographie clean-up and analysis by a column-switching technique. In Modified Nucleosides in Cancer and Normal Metabolism, pp. C115-C145 [Gehrke, CW and Kuo, KC, editors]. Journal of Chromatography Library, 45, Amsterdam: Elsevier.Google Scholar
Schlimme, E, Boos, K-S, Frister, H, Pabst, K, Raezke, K-P & Wilmers, B (1986) Gruppenselektive Hochleistungsflüssigkeitschromatographie von Ribonucleosiden in Milch. Milchwissenschaft 41, 757762.Google Scholar
Schlimme, E, Boos, K-S, Schwarzenau, E, Frister, H, Ott, FG, Raezke, K-P & Wilmers, B (1990) Dual column HPLC analysis of modified ribonucleosides as urinary pathobiochemical markers in clinical research. Nucleosides & Nucleotides 9, 407410.CrossRefGoogle Scholar
Schlimme, E, Kiesner, C, Lorenzen, PChr & Martin, D (1998) Influence of heat treatment of milk on the activities of the indigenous milk enzymes alkaline phosphatase and adenosine deaminase International Dairy Federation-Bulletin No. 332, 2531.Google Scholar
Schlimme, E, Lorenzen, PChr, Martin, D, Meisel, H &, Thormählen, K (1997 a) Differenzierung von Buttersorten. Kieler Milchwirtschaftliche Forschungsberichte 49, 135145.Google Scholar
Schlimme, E, Lorenzen, PChr, Martin, D &, Thormählen, K (1996 b) Analytical differentiation of butter types by specific compositional parameters of the aqueous butter phase. Milchwissenschaft 51, 139143.Google Scholar
Schlimme, E & Martin, D (1999) Nucleotid-Supplementierung von Säuglingsnahrung. Kieler Milchwirtschaftliche Forschungsberichte 51, 215224.Google Scholar
Schlimme, E, Martin, D, Meisel, H, Schneehagen, K, Hoffmann, S, Sievers, E, Ott, FG &, Raezke, K-P (1997) Species-specific composition pattern of milk ribonucleosides and -nucleotides: chemical and physiological aspects. Kieler Milchwirtschaftliche Forschungsberichte 49, 305326.Google Scholar
Schlimme, E, Ott, FG & Kiesner, C (1994) Reaction kinetics of heat induced formation of N6-methyladenosine in milk. International Dairy Journal 4, 617627.CrossRefGoogle Scholar
Schlimme, E, Ott, FG, Kiesner, C & Biewendt, HG (1993) Heat-dependent generation of modified ribonucleosides in milk in the temperature range 40–150°C. International Dairy Federation Special Issue 9303, 5266.Google Scholar
Schlimme, E, Raezke, K-P & Ott, FG (1991) Ribonucleosides as minor milk constituents. Zeitschrift für Ernährungswissenschaft 30, 138152.CrossRefGoogle ScholarPubMed
Schlimme, E, Raezke, K-P, Ott, FG, Schneehagen, K (1996 a) Ribonucleosides as minor milk constituents: Dependence of nucleoside composition on mammalian species and lactation stage. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 6986 [Gil, A and Uauy, R, editors]. Granada: Abbott Laboratories.Google Scholar
Schlimme, E & Schneehagen, K (1995) Ribonucleosides in human milk -Concentration profiles of these minor constituents as a function of the nursing time. Zeitschrift für Naturforschung 50, 105113.CrossRefGoogle ScholarPubMed
Schlimme, E, Schneehagen, K & Ott, FG (1990 b) Differenzierung von Buttersorten mit Hilfe der Butterserum-Ribonucleoside. Milchwissenschaft 45, 654657.Google Scholar
Schneehagen, K & Schlimme, E (1992) Ribonucleoside: Minore Inhaltsstoffe der Humanmilch. Kieler Milchwirtschaftliche Forschungsberichte 44, 6774.Google Scholar
Schwarzenau, E, Schlimme, E, Boos, K-S, Wilmers, B, Raezke, K-P, Ott, FG, Hilfrich, J & Schneider, J (1990) Ribonucleosidausscheidungsmuster bei Mammakarzinompatientinnen. Tumor Diagnostik & Therapie 11, 198203.Google Scholar
Souci, SW, Fachmann, W & Kraut, H (1994) In Food Composition and Nutrition Tables 5th edition. Boca Raton: CRC Press, Medpharm Scientific Publishers.Google Scholar
Sugawara, M, Sato, N, Nakano, T, Idota, T & Nakajima, I (1995) Profile of nucleotides and nucleosides in human milk. Journal of Nutritional Science and Vitaminology 41, 409418.CrossRefGoogle ScholarPubMed
Tiemeyer, W, Stohrer, M & Giesecke, D (1984) Metabolites of nucleic acids in bovine milk. Journal of Dairy Science 67, 723728.CrossRefGoogle ScholarPubMed
Topp, H, Groß, H, Heller-Schöch, G &, Schöch, G (1993) Determination of N6-threoninocarbonyladenosine N2,N2-dimethylguanosine, pseudouridine and other ribonucleosides in human breast milk. Nucleosides & Nucleotides 12, 585596.CrossRefGoogle Scholar
Uauy, R & and, ELebenthal (1989) Dietary nucleotides and requirements in early life. In Textbook of Gastroenterology and Nutrition in Infancy, 2nd edition, pp. 265280 [Lebenthal, E, editor]. New York: Raven Press.Google Scholar
Uau, R, Quan, R & Gil, A (1996) Nucleotides in infant nutrition. In Nutritional and Biological Significance of Dietary Nucleotides and Nucleic Acids, pp. 169180 [Gil, A and Uauy, R, editors] Granada: Abbott Laboratories.Google Scholar
Uauy, R, Stringel, G, Thomas, R & Quan, R (1990) Effect of dietary nucleosides on growth and maturation of the developing gut in the rat. Journal of Pediatric Gastroenterology and Nutrition 10, 497503.Google ScholarPubMed
Ullman, B, Patrick, J & McCartan, K (1987) Expression of the high-affinity purine nucleobase transporter in mutant mouse S49 cells does not require a functional wild-type nucleoside-nucleobase transporter. Molecular and Cellular Biology 7, 97103.Google Scholar
Van Buren, CT & Rudolph, F (1997) Dietary nucleotides: A conditional requirement. Nutrition 13, 470472.CrossRefGoogle ScholarPubMed
Vijayalakshmi, D, Dagino, L, Belt, JA, Gati, WP, Cass, CE & Paterson, ARP (1992) Cells express equilibrative, inhibitor-sensitive nucleoside transport activity and lack two parental nucleoside transport activities. Journal of Biological Chemistry 267, 1695116956.CrossRefGoogle ScholarPubMed
Williams, TC & Jarvis, SM (1991) Multiple sodium dependent nucleoside transport systems in bovine renal brush-border membrane vesicles. Biochemical Journal 274, 2733.CrossRefGoogle ScholarPubMed
Wright, SC, Zhong, J & Larrick, JW (1994) Inhibition of apoptosis as a mechanism of tumor promotion. The FASEB Journal 8, 654660.CrossRefGoogle ScholarPubMed
Ziv, G & Heavner, JE (1984) Permeability of the blood-milk barrier to methylene blue in cows and goats. Journal of Veterinary Pharmacology and Therapeutics 7, 5559.CrossRefGoogle ScholarPubMed
Ziv, G & Sulman, FG (1975) Absorption of antibiotics by the bovine udder. Journal of Dairy Science 58, 16371644.CrossRefGoogle ScholarPubMed