口服他莫昔芬、托瑞米芬、脱氢表雄酮和vorozole对大鼠子宫组织形态学的影响。

K P Nephew, E Osborne, R A Lubet, C J Grubbs, S A Khan
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引用次数: 16

摘要

他莫昔芬、托瑞米芬、脱氢表雄酮和vorozole抑制啮齿动物乳腺癌模型的肿瘤生长,是很有前途的用于乳腺癌发展的化疗药物。在本研究中,研究了这些药物对成熟卵巢完整大鼠(n = 380)口服后子宫组织形态学的影响。动物只饲喂日粮(对照组)、他莫昔芬(0.4和1 mg/kg日粮);10 mg/kg体重(每日灌胃)、托瑞米芬(3-30 mg/kg体重)、脱氢表雄酮(24-2000 mg/kg体重)或vorozole (0.08-1.25 mg/kg体重(每日灌胃),持续28天,然后处死或返回基础饲粮,21天后处死。用托瑞米芬(所有剂量)或他莫昔芬(1和10 mg/kg)治疗28天可降低(P
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of oral administration of tamoxifen, toremifene, dehydroepiandrosterone, and vorozole on uterine histomorphology in the rat.

Tamoxifen, toremifene, DHEA, and vorozole inhibit tumor growth in rodent mammary carcinoma models and are promising chemotherapeutic agents for use against breast cancer development. In the present study, the effect of these agents on uterine histomorphology following oral administration to mature ovary-intact rats (n = 380) was examined. Animals received diet only (control), tamoxifen (0.4 and 1 mg/kg of diet; 10 mg/kg BW by daily gavage), toremifene (3-30 mg/kg of diet), DHEA (24-2000 mg/kg of diet), or vorozole (0.08-1.25 mg/kg BW by daily gavage) for 28 days and were either sacrificed or returned to a basal diet and then sacrificed 21 days later. Treatment with toremifene (all doses) or tamoxifen (1 and 10 mg/kg) for 28 days produced a decrease (P<0.05) in overall uterine size and myometrial thickness; however, uterine luminal and glandular epithelia cell height increased (P<0.05) compared with control. These compartmentalized uterotrophic and antiestrogenic effects of toremifene and tamoxifen were still apparent after 21 days post-treatment. Administration of DHEA (2000 mg/kg of diet) for 28 days had dramatic uterotrophic effects, increasing (P<0.05) overall uterine size and stimulating all three uterine compartments (epithelia, stroma, and myometrium). The other doses of DHEA, however, were not uterotrophic. Interestingly, after removal of DHEA from the diet, uterine weight and myometrial thickness decreased (P<0.05). Vorozole (1.25 mg/kg) administration for 28 days had differential, compartmentalized uterine effects, producing an increase (P<0.05) in epithelial cell height, a decrease (P<0.05) in stromal size, but no change in myometrial thickness. After 21 days postadministration of vorozole, luminal epithelial cell height was increased (P<0.05) compared with control. The data suggest that oral administration of tamoxifen, toremifene, DHEA, and vorozole results in differential, compartmentalized effects in the uterus that are highly dependent on treatment dose. The data may have implications for risk assessment of these agents prior to administration to healthy, cancer-free women.

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