Lifetime Assessment of Dietary Nucleotides Consumption in Sprague-Dawley Rats

Meihong Xu^{1, 2}, Rui Liang^{1, 2}, Qianying Guo^{1, 2}, Shuangjia Wang^{1, 2}, Ming Zhao^{1, 2}, Zhaofeng Zhang^{1, 2}, Junbo Wang^{1, 2} and Yong Li^{1, 2,}

¹Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR China

²Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing, PR China

Cite this paper:
Meihong Xu, Rui Liang, Qianying Guo, Shuangjia Wang, Ming Zhao, Zhaofeng Zhang, Junbo Wang and Yong Li. Lifetime Assessment of Dietary Nucleotides Consumption in Sprague-Dawley Rats. Journal of Food and Nutrition Research. 2014; 2(11):806-813. doi: 10.12691/jfnr-2-11-8

Abstract

To assess the long-term toxicity and carcinogenicity of dietary nucleotides (NTs), Sprague-Dawley rats were administered the NTs for life-through with the dose of 0, 0.01%, 0.04%, 0.16% and 0.64%. With the exception of several groups, the results showed no significant differences in weight gain, clinical symptoms data, blood indicators, and Non-neoplastic lesions frequencies. NTs have dramatically increased the food consumption of both sexes (P<0.05). Meanwhile, NTs decreased spontaneous tumor incidence of both sexes, notably the male rats (P<0.05). The occurrence of all malignant and mammary tumors in NTs-treated females was lower than those in controls (P<0.05). In comparison with the control group, the incidence of death from malignant and systemic tumors were obviously decreased in the NTs-treated groups (P<0.01). Moreover, our results showed that a higher percentage of rats in the NTs-treated groups died of non-neoplastic lesions compared with control. In conclusion, dietary nucleotides are not toxic or carcinogenic in rats up to 0.64% for all the life, and 0.64% was an unobservable effect dose.

Keywords:
dietary nucleotides safety lifelong Spontaneous Tumor Incidence Sprague-Dawley rat

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Fontana L, Moreira E, Torres MI, et al. Dietary nucleotides correct plasma and liver microsomal fatty acid alterations in rats with liver cirrhosis induced by oral intake of thioacetamide. J Hepatol. 1998; 28 (4): 662-9.
[2]	Jyonouchi H, Sun S, Winship T, et al. Dietary ribonucleotides increase antigen-specific type 1 T-helper cells in the regional draining lymph nodes in young BALB/cJ mice. Nutrition. 2003; 19 (1): 41-6.
[3]	Yokoyama H, Fujiwara H, Watanabe H. Dietary nucleosides and nucleotides do not affect tumor incidence but reduce amyloidosis incidence in B6C3F1 mice irradiated with californium-252. Nutrition. 2004; 20 (4): 383-9.
[4]	Frankic T, Pajk T, Rezar V, et al. The role of dietary nucleotides in reduction of DNA damage induced by T-2 toxin and deoxynivalenol in chicken leukocytes. Food Chem Toxicol. 2006; 44 (11): 1838-44.
[5]	Tahmasebi KA, Keyvanshokooh S, Nematollahi A, et al. Dietary administration of nucleotides to enhance growth, humoral immune responses, and disease resistance of the rainbow trout (Oncorhynchus mykiss) fingerlings. Fish Shellfish Immunol. 2011; 30 (1): 189-93.
[6]	Sauer N, Bauer E, Vahjen W,et al. Nucleotides modify growth of selected intestinal bacteria in vitro. Livestock Science. 2010; 133 (1): 161-3.
[7]	Lopez-Navarro AT, Ortega MA, Peragon J, et al. Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats. Gastroenterology. 1996; 110 (6): 1760-9.
[8]	Iwasa Y, Iwasa M, Ohmori Y, et al. The effect of the administration of nucleosides and nucleotides for parenteral use. Nutrition. 2000; 16 (7-8): 598-602.
[9]	Sanchez PA, Gil A. Nucleotides as semiessential nutritional components. Br J Nutr 2002; 87 (Suppl 1): S135-7.
[10]	Singhal A, Kennedy K, Lanigan J, et al. Dietary Nucleotides and Early Growth inFormula-Fed Infants: A Randomized Controlled Trial. Pediatrics. 2010; 126 (4): e946-53.
[11]	Anisimov VN. Life span extension and cancer risk: myths and reality. Exp Gerontol. 2001; 36 (7): 1101-36.
[12]	Cavigelli SA, Bennett JM, Michael KC, et al. Female temperament, tumor development and life span: relation to glucocorticoid and tumor necrosis factor alpha levels in rats. Brain Behav Immun. 2008; 22 (5):727-35.
[13]	Mesia-Vela S, Sanchez RI, Roberts KG, et al. Dietary clofibrate stimulates the formation and size of estradiol-induced breast tumors in female August-Copenhagen Irish (ACI) rats. Toxicology. 2008; 246 (1): 63-7.
[14]	Gart J, Krewski D, Lee PN, et al. IARC Scientific Publications Number 79: Statistical Methods in Cancer Research, Vol. III-The Design and Analysis of Long-Term Animal Experiments. International Agency for Research on Cancer, Lyon, France.
[15]	Peto R, Pike MC, Day NE, et al. Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. IARC Monogr Eval Carcinog Risk Chem Hum Suppl. 1980; (2 Suppl): 311-426.
[16]	Meihong Xu, Rui Liang, Qianying Guo, et al. Dietary nucleotides Extend the Life Span in Sprague-Dawley Rat. The Journal of Nutrition, Health and Aging. 2013; 17 (3): 223-9.
[17]	Baldrick P. Carcinogenicity evaluation: comparison of tumor data from dual control groups in the Sprague-Dawley rat. Toxicol Pathol. 2005; 33 (2): 283-91.
[18]	Nakazawa M, Tawaratani T, Uchimoto H, et al. Spontaneous neoplastic lesions in aged Sprague-Dawley rats. Exp Anim. 2001; 50 (2): 99-103.
[19]	Baldrick P, Reeve L. Carcinogenicity evaluation: comparison of tumor data from dual control groups in the CD-1 mouse. Toxicol Pathol. 2007; 35 (4): 562-9.
[20]	Dirx MJ, Zeegers MP, Dagnelie PC, et al. Energy restriction and the risk of spontaneous mammary tumors in mice: a meta-analysis. Int J Cancer. 2003; 106 (5): 766-70.
[21]	Inal ME, Kanbak G, Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin Chim Acta. 2001; 305 (1-2): 75-80.
[22]	Niedernhofer LJ, Daniels JS, Rouzer CA, et al. Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells. J Biol Chem. 2003; 278 (33): 31426-33.
[23]	Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993; 90 (1): 7915-22.
[24]	Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med. 1990; 8 (6): 583-99.
[25]	Van RH, Ikeno Y, Hamilton M, et al. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics. 2003; 16 (1): 29-37.