Tamano S, Tanaka H, Kawabe M, Asakawa E, Sano M, Shioya S, Shirai T, Fukushima S
First Department of Pathology, Nagoya City University Medical School, Japan.
J Toxicol Environ Health. 1993 May;39(1):43-58. doi: 10.1080/15287399309531735.
Calcium/magnesium salts of L-glutamate and L-ascorbate were tested for modification potential using a rat multiorgan carcinogenesis bioassay. Following sequential treatment with three different carcinogens (diethylnitrosamine, N-methylnitrosourea, and dihydroxydi-N-propylnitrosamine) over a 4-wk period, rats were given diet containing 5% monocalcium di-L-glutamate tetrahydrate (Ca-glutamate), 2.5% monomagnesium di-L-glutamate tetrahydrate (Mg-glutamate), 5% L-glutamic acid, 5% monocalcium di-L-ascorbate dihydrate (Ca-ascorbate), 2.5% monomagnesium di-L-ascorbate dihydrate (Mg-ascorbate), or 5% L-ascorbic acid for 16 wk. Body weight increase was slightly suppressed in the groups receiving Ca-ascorbate, Mg-ascorbate, and ascorbic acid supplementation after the carcinogen treatments. While administration of Ca-glutamate or Ca-ascorbate raised urinary pH, ascorbic acid values were decreased. Concentrations of calcium and magnesium ions in the urine increased after ingestion of Ca-glutamate or Ca-ascorbate, and Mg-glutamate or Mg-ascorbate, respectively, but phosphorus levels decreased in all groups given calcium and magnesium salts. No consistent treatment-related changes in the concentrations of sodium or potassium ions in the urine were detected. Histopathological investigation at wk 20 did not demonstrate any modification of tumorigenesis with regard to the incidence of frequency of lesions developing in the various target organs/tissues. The present results thus revealed no apparent enhancement of carcinogenesis at any site, including the urinary system, by calcium or magnesium salts using the present rat multiorgan carcinogenesis bioassay.
使用大鼠多器官致癌生物测定法测试了L-谷氨酸和L-抗坏血酸的钙/镁盐的潜在修饰作用。在4周的时间内依次用三种不同的致癌物(二乙基亚硝胺、N-甲基亚硝基脲和二羟基二-N-丙基亚硝胺)处理大鼠后,给大鼠喂食含有5%一水合二-L-谷氨酸钙四水合物(钙-谷氨酸)、2.5%一水合二-L-谷氨酸镁四水合物(镁-谷氨酸)、5% L-谷氨酸、5%一水合二-L-抗坏血酸钙二水合物(钙-抗坏血酸)、2.5%一水合二-L-抗坏血酸镁二水合物(镁-抗坏血酸)或5% L-抗坏血酸的饲料,持续16周。在致癌物处理后,接受钙-抗坏血酸、镁-抗坏血酸和抗坏血酸补充剂的组中体重增加略有抑制。虽然给予钙-谷氨酸或钙-抗坏血酸会提高尿液pH值,但抗坏血酸值会降低。摄入钙-谷氨酸或钙-抗坏血酸后,尿液中钙和镁离子的浓度分别增加,而摄入镁-谷氨酸或镁-抗坏血酸后也有同样情况,但在所有给予钙盐和镁盐的组中磷水平均降低。未检测到与处理相关的尿液中钠或钾离子浓度的一致变化。在第20周进行的组织病理学检查未显示在各种靶器官/组织中发生的病变频率或发生率方面肿瘤发生有任何改变。因此,目前的结果表明,使用本大鼠多器官致癌生物测定法,钙盐或镁盐在任何部位,包括泌尿系统,均未显示出明显的致癌增强作用。