SEX HORMONE-DEPENDENT RENAL-CELL CARCINOGENESIS INDUCED BY FERRIC NITRILOTRIACETATE IN WISTAR RATS
SEX HORMONE-DEPENDENT RENAL-CELL CARCINOGENESIS INDUCED BY FERRIC NITRILOTRIACETATE IN WISTAR RATS
复制标题
DOI：
10.1111/j.1349-7006.1995.tb03022.x
复制
发表时间：
1995-11-01
期刊：
影响因子：
--
通讯作者：
OKADA, S
中科院分区：
文献类型：
--
作者：
DEGUCHI, J;MIYAMOTO, M;OKADA, S
次氮基三乙酸铁（Fe-NTA）是一种铁螯合物，可引起大鼠和小鼠肾近曲小管脂质过氧化损伤，导致肾细胞癌（RCC）的发生。肾细胞癌的发病率和脂质过氧化程度男性高于女性。在本研究中，去势或卵巢切除，和性激素治疗的影响，铁NTA诱导的大鼠肾癌的发生进行了检查。雄性和雌性Wister大鼠均分为5组。在第1组中，将大鼠假手术并腹膜内（i. P.）次氮基三乙酸酯（NTA）。在第2组中，用Fe-NTA（5-10 mg铁/kg/天，i. p.）处理假手术大鼠。用Fe-NTA治疗的去势或卵巢切除大鼠作为第3组。第4组或第5组以与第3组相同的方式处理，但另外接受睾酮（第4组）或雌二醇（第5组）。手术后4周开始NTA、Fe-NTA或性激素治疗。NTA或Fe-NTA治疗12周，性激素治疗10个月。给药10个月后，对所有大鼠进行尸检，并对双肾进行组织病理学检查。在NTA治疗组中，肾脏没有病理变化。在Fe-NTA处理组（第2-5组）中，睾酮处理或卵巢切除增加了RCC的发生率，而雌二醇处理或去势降低了RCC的发生率（男性：假手术、去势和睾酮处理>去势>去势和雌二醇处理，女性：卵巢切除和睾酮处理>卵巢切除>假手术、卵巢切除和雌二醇处理）。这些结果表明，在由Fe-NTA诱导的RCC的发病率中观察到的性别差异依赖于性激素。
Ferric nitrilotriacetate (Fe-NTA), an iron chelate, induces necrosis of renal proximal convoluted tubules as a consequence of lipid peroxidation, and a high incidence of renal cell carcinoma (RCC) is also observed in rats and mice. The incidence of RCC and the extent of lipid peroxidation are greater in males than females. In the present study, the effects of castration or ovariectomy, and sex hormone treatment on Fe-NTA-induced renal carcinogenesis in rats were examined. Male and female Wister rats were each divided into 5 groups. In group 1, rats were sham-operated and treated intraperitoneally (i.p.) with nitrilotriacetate (NTA). In group 2, sham-operated rats were treated with Fe-NTA (5-10 mg iron/kg/day, i.p.). Castrated or ovariectomized rats treated with Fe-NTA served as group 3. Group 4 or 5 was treated in the same way as group 3, but in addition received either testosterone (group 4) or estradiol (group 5). NTA, Fe-NTA or sex hormone treatments were initiated 4 weeks after the operation. NTA or Fe-NTA treatments were conducted for 12 weeks, and sex hormones were administered for 10 months. After 10 months of treatment, all rats were autopsied and both kidneys were examined histopathologically. In NTA-treated groups, there was no pathological change in the kidneys. In Fe-NTA-treated groups (groups 2-5), testosterone treatment or ovariectomy increased the incidence of RCC, and estradiol treatment or castration decreased the incidence of RCC (male: sham operation, castration and testosterone treatment > castration > castration and estradiol treatment, female: ovariectomy and testosterone treatment > ovariectomy > sham operation, ovariectomy and estradiol treatment). These results indicate that sex differences observed in the incidence of RCC induced by Fe-NTA are dependent upon sex hormones.