Kitamura M, Konishi N, Kitahori Y, Fukushima Y, Yoshioka N, Hiasa Y
Second Department of Pathology, Nara Medical University, Japan.
Toxicol Pathol. 1996 Sep-Oct;24(5):573-9. doi: 10.1177/019262339602400506.
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.
尽管发生率相对较低,但在为期两年的长期生物测定中,给Fischer-344(F-344)大鼠同时用天冬氨酸钠和甘氨酸处理后,已观察到肾盂和膀胱的增生。在本研究中,在雄性和雌性F-344/DuCrj大鼠中研究了这些氨基酸对N-丁基-N-(4-羟丁基)亚硝胺(BBN)引发的泌尿系统病变发展的影响。实验开始时6周龄的雌雄F-344大鼠接受0.05%BBN处理4周,然后在接下来的36周内,用饮用水中浓度为5.0%的一种氨基酸进行处理。在接受BBN处理后再用天冬氨酸钠处理的组中,肾盂中常伴有坏死和矿化的增生性病变在两性中均增加,而用甘氨酸处理的组则未增加。同一组显示膀胱肿瘤的发生率更高,尿液pH值和钠浓度升高,肌酐和尿酸降低,但未伴随结晶。这些结果表明天冬氨酸钠对大鼠泌尿系统致癌作用有明显的促进作用。其对肾盂和膀胱的作用机制可能不同。