Promoting Effect of Monosodium Aspartate,But Not Glycine,on Renal Pelvis and Urinary Bladder Carcinogenesis in Rat Induced by N-Butyl-N-(4-Hydroxybutyl)nitrosamine
Free accessOtherFirst published online September, 1996
Promoting Effect of Monosodium Aspartate,But Not Glycine,on Renal Pelvis and Urinary Bladder Carcinogenesis in Rat Induced by N-Butyl-N-(4-Hydroxybutyl)nitrosamine
Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.
Ayres PH, Shinohara Y., and Frith CH (1985). Morphological observations on the epithelium of the developing urinary bladder of the mouse and the rat. J. Urol. 133: 506-512.
2.
Cohen SM (1991). Analysis of modifying factors in chemical carcinogenesis . In: Progress in Experimental Tumor Research: Modification of Tumor Development in Rodents, N Ito and H Sugano (eds). S Karger, New York, pp. 21-40.
3.
Cohen SM (1995). Role of urinary physiology and chemistry in bladder carcinogenesis. Food Chem. Toxic. 33: 715-730.
4.
Cohen SM, Cano M., Garland EM, St John M., and Arnold LL (1995). Urinary and urothelial effects of sodium salts in male rats. Carcinogenesis16: 343-348.
5.
Cohen SM and Ellwein LB (1990). Cell proliferation in carcinogenesis. Science249: 1907-1911.
6.
Cohen SM, Garland EM, Cano M., St John M., Khachab M., Wehner JM, and Arnold LL (1995). Effects of sodium ascorbate, sodium saccharin and ammonium chloride on the male rat urinary bladder. Carcinogenesis16: 2743-2750.
7.
Frith CH, Eighmy JJ, Fukushima S., Cohen SM, Squire RA, and Chandra M. (1995). Proliferative lesions of the lower urinary tract in rats, URG-2. In: Guides for Toxicologic Pathology. STP/ARP/ AFIP, Washington, D.C., pp. 1-13.
8.
Frith CH, Greenman DL, and Cohen SM (1994). Urinary bladder carcinogenesis in the rodent. In: Carcinogenesis, MP Waalkes and JM Ward (eds). Raven Press, New York, pp. 161-198.
9.
Fukushima S. (1991). Modification of tumor development in the urinary bladder. Prog. Exp. Tumor Res. 33: 154-174.
10.
Fukushima S. , Tamano S., Shibata M., Kurata Y., Hirose M., and Ito N. (1988). The role of urinary pH and sodium ion concentration in the promotion stage of two-stage carcinogenesis of the rat urinary bladder. Carcinogenesis9: 1203-1206.
11.
Hashimoto Y. and Kitagawa HS (1974). In vitro neoplastic transformation of epithelial cells of rat urinary bladder by nitrosamine. Nature (London) 252: 497-499.
12.
Hashimoto Y. , Suzuki E., and Okada M. (1972). Induction of urinary bladder tumors in ACI-N rats by butyl(3-carboxypropyl)nitrosamine, a major urinary metabolite of butyl(4-hydroxybutyl)nitrosamine. Gann63: 637-638.
13.
Hiasa Y., Kitahori Y., Konishi N., Nakaoka S., and Nishioka H. (1992). Carcinogenicity study in rats of phytic acid "Daiichi", a natural food additive. Food Chem. Toxic.30: 117-125.
14.
Hirose M., Fukushima S., Hananouchi M., Shirai T., Ogiso T., Takahashi M., and Ito N. (1976). Different susceptibilities of the urinary bladder epithelium of animal species to three nitroso compounds. Gann67: 175-189.
15.
International Agency for Research on Cancer (1980). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 22. Some Non-nutritive Sweetening Agents. International Agency for Research on Cancer, Lyon, France.
16.
Ito N. and Fukushima S. (1986). Carcinogenesis, urinary tract, rat. In: Monographs on Pathology of Laboratory Animals. Urinary System, TC Jones, U Mohr , and RD Hunt (eds). Springer-Verlag, Berlin, Heidelberg, New York, pp. 317-322.
17.
Ito N., Hiasa Y., Tamai A., Okajima E., and Kitamura H. (1969). Histogenesis of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in rats. Gann60: 401-410.
18.
Kitahori Y. , Kitamura M., Konishi N., Matsuda H., Tao M., Matsui E., Naito H., Nakamura Y., and Hiasa Y. (1996). Carcinogenicity study of monosodium aspartate in Fischer 344 rats; 100 weeks treatment. J. Toxicol. Pathol. 9: 161-168.
19.
Kitahori Y. , Konishi N., Hayashi I., Nakahashi K., Kitamura M., Nakamura Y., Matsuda H., Fukushima Y., Yoshioka N., and Hiasa Y. (1994). Carcinogenicity study of glycine in Fischer 344 rats. J. Toxicol. Pathol. 7: 471-480.
20.
Melnick RL, Boorman GA, Haseman JK, Montali, RJ, and Huff J. (1984). Urolithiasis and bladder carcinogenicity of melamine in rodents. Toxicol. Appl. Pharmacol. 72: 292-303.
21.
Messing EM (1990). Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma. Cancer Res. 50: 2530-2537.
22.
Mirvish SS, Haight R., Nickols J., Deshpande A., McWilliams N., Babcock DM, and Morris CR (1993). Creatinine nitrosation to yield 5-oxocreatinine 5-oxime and 1-methyl-5-oxohydantoin 5-oxide: Reaction rates, identification of syn and anti oxime isomers and their interconversion by nitrite. J. Agricul. Food Chem. 41: 2051-2055.
23.
Nakanowatari J., Fukushima S., Imaida K., Ito N., and Nagase S. (1988). Strain differences in N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis in rats. Jpn . J. Cancer Res. 79: 453-459.
24.
Okajima E., Hiramatsu T., Hirao K., Ijuin M., Hirao Y., Babaya K., Ikuma S., Ohhara S., Shiomi T., Hijioka T., and Ohishi H. (1981). Urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs. Cancer Res. 41: 1958-1966.
25.
Ritts RF (1971). Metabolism of amino acids by the perfused rat kidney. Am. J. Physiol. 220: 862-867.
26.
Schoening GP , Goldenthal EI, Geil RG, Frith CH, Richter WR, and Carlborg FW (1985). Evaluation of the dose response and in utero exposure to saccharin in the rat. Food Chem. Toxicol. 23: 475-490.
27.
Thomas RC (1989). Cell growth factors. Bicarbonate and pH: Responses . Nature (London)337: 601.
