Morton Laura Dill, Youssef Ashraf F, Lloyd Eric, Kiorpes Anthony L, Goldsworthy Thomas L, Fort Farrel L
Pharmacia Corporation, Skokie, Illinois 60077, USA.
Toxicol Pathol. 2002 Sep-Oct;30(5):559-64. doi: 10.1080/01926230290105794.
This study examined the response of the Eker rat to nephrotoxic compounds and to genotoxic nonrenal carcinogens. Groups of male Eker rats received either no treatment; a vehicle treatment; treatment with a noncarcinogenic nephrotoxin (aluminum nitrilotriacetate, 2 mg/kg/day of aluminum, intraperitoneally, 3 days per week or cyclosporine A, 30 mg/kg/day, orally by gavage, 7 days/week); or treatment with a genotoxic nonrenal carcinogen (furan, 8 mg/kg/day, orally by gavage, 5 days/week or 2,4-diaminotoluene, 6.5 mg/kg/day, orally by gavage, 7 days/week or 2-nitropropane, 89 mg/kg/day, orally by gavage, 3 days/week). Duration of treatment was 4 and/or 6 months. Tissues from the Eker rats were evaluated microscopically and numbers of proliferative renal lesions were counted. Administration of nephrotoxic compounds (Al-NTA and cyclosporine) significantly increased the number of preneoplastic and neoplastic renal lesions in the Eker rat compared to concurrent vehicle controls. The genotoxic nonrenal carcinogens had no consistent effect on numbers of preneoplastic or neoplastic renal lesions and did not produce neoplasms in the expected target organ (liver).
本研究考察了埃克大鼠对肾毒性化合物和遗传毒性非肾致癌物的反应。将雄性埃克大鼠分组，分别给予以下处理：不进行处理；给予赋形剂；给予非致癌性肾毒素（次氮基三乙酸铝，铝含量为2毫克/千克/天，腹腔注射，每周3天，或环孢素A，30毫克/千克/天，经口灌胃，每周7天）；或给予遗传毒性非肾致癌物（呋喃，8毫克/千克/天，经口灌胃，每周5天，或2,4-二氨基甲苯，6.5毫克/千克/天，经口灌胃，每周7天，或2-硝基丙烷，89毫克/千克/天，经口灌胃，每周3天）。治疗持续时间为4个月和/或6个月。对埃克大鼠的组织进行显微镜评估，并对增殖性肾损伤的数量进行计数。与同期给予赋形剂的对照组相比，给予肾毒性化合物（次氮基三乙酸铝和环孢素）显著增加了埃克大鼠癌前和肿瘤性肾损伤的数量。遗传毒性非肾致癌物对癌前或肿瘤性肾损伤的数量没有一致的影响，并且在预期的靶器官（肝脏）中未产生肿瘤。
