Kitahori Y, Shimoyama T, Ohshima M, Matsuki H, Hashimoto H, Minami S, Konishi N, Hiasa Y
First Department of Pathology, Nara Medical University, Japan.
Cancer Lett. 1988 Dec 1;43(1-2):105-10. doi: 10.1016/0304-3835(88)90221-2.
The effects of trisodium nitrilotriacetate monohydrate (Na3 NTA.H2O) nitrilotriacetic acid (H3NTA) and ammonium chloride (NH4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na3NTA.H2O, Na3NTA.H2O plus NH4Cl, H3NTA, H3NTA plus NH4Cl, or without these chemicals for 28 weeks. Na3NTA.H2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na3NTA.H2O, without the initiation, itself induced papillary or nodular (PN)-hyperplasia. H3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na3NTA.H2O was more effective than H3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.
研究了三水合次氮基三乙酸三钠（Na3NTA·H2O）、次氮基三乙酸（H3NTA）和氯化铵（NH4Cl）对两阶段膀胱癌发生的影响。通过在饮用水中给雄性Wistar大鼠施用0.2%的N-双（2-羟丙基）-亚硝胺（DHPN）2周来启动致癌过程，然后用含有Na3NTA·H2O、Na3NTA·H2O加NH4Cl、H3NTA、H3NTA加NH4Cl的基础饲料或不含这些化学物质的基础饲料对动物进行处理28周。Na3NTA·H2O显著增加了膀胱肿瘤性和癌前病变的发生率。此外，在没有启动致癌过程的情况下，用Na3NTA·H2O处理本身会诱导乳头状或结节状（PN）增生。H3NTA仅使由DHPN启动的大鼠癌前膀胱病变（PN增生）的发生率略有增加，且无统计学意义。尿液pH值和钠离子浓度的升高与肿瘤发展的促进相关。这些数据表明，就促进潜能而言，Na3NTA·H2O比H3NTA更有效，并且尿液pH值和钠离子浓度的变化在这些化学物质增强膀胱肿瘤发生中起重要作用。
