Martin G, Davio C, Rivera E, Melito G, Cricco G, Andrade N, Caro R, Bergoc R
Laboratorio de Radioisótopos, Cátedra de Física, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, República Argentina.
Cancer Invest. 1997;15(1):8-17. doi: 10.3109/07357909709018912.
The purpose of this work was to determine the hormone dependence of mammary tumors induced in Sprague-Dawley rats by three intraperitoneal injections of N-nitroso-N-methylurea at 50, 80, and 110 days of age. Two experimental designs were carried out: (a) Ten days before the first NMU injection, 130 rats were divided into 13 batches and randomly assigned to the following treatments: control, ovariectomy (OVX), tamoxifen (TAM), bromocriptine (BROM), haloperidol (HAL), estradiol (E2), progesterone (Pg), OVX + BROM, TAM + BROM, OVX + HAL, TAM + HAL, OVX + TAM, and E2 + BROM. After 150 days of treatment the following growth parameters were determined: latency period (LP), mean tumor number per rat (n/t), and tumor incidence (TI). LP was significantly increased (p < 0.05) only by Pg and TAM + BROM. The n/t was significantly decreased (p < 0.05) by all treatments except HAL. TI was significantly reduced by OVX, TAM, BROM, and their combinations, (b) Rats bearing ip-NMU-induced mammary tumors were divided into 7 batches and assigned to the following treatments: control, OVX, TAM, BROM, HAL, OVX + BROM, and TAM + BROM. Tumor growth was assessed up to 60 days of treatment; only OVX, TAM and their combination with BROM were able to produce tumor regression. These results support the essential role of E2 and prolactin in the promotion stage of carcinogenesis. However, for established tumors, growth becomes more independent from hormone influence, in particular from prolactin deprivation. We conclude that this model seems suitable for studying the mechanisms underlying the evasion of hormonal control of tumor growth.
本研究的目的是确定在50、80和110日龄时通过腹腔注射三次N-亚硝基-N-甲基脲诱导的Sprague-Dawley大鼠乳腺肿瘤的激素依赖性。进行了两种实验设计：(a) 在首次注射NMU前10天，将130只大鼠分为13组，并随机分配到以下处理组：对照组、卵巢切除术（OVX）、他莫昔芬（TAM）、溴隐亭（BROM）、氟哌啶醇（HAL）、雌二醇（E2）、孕酮（Pg）、OVX + BROM、TAM + BROM、OVX + HAL、TAM + HAL、OVX + TAM和E2 + BROM。治疗150天后，测定以下生长参数：潜伏期（LP）、每只大鼠的平均肿瘤数（n/t）和肿瘤发生率（TI）。仅Pg和TAM + BROM显著增加了LP（p < 0.05）。除HAL外，所有处理均显著降低了n/t（p < 0.05）。OVX、TAM、BROM及其组合显著降低了TI。(b) 将腹腔注射NMU诱导的乳腺肿瘤大鼠分为7组，并分配到以下处理组：对照组、OVX、TAM、BROM、HAL、OVX + BROM和TAM + BROM。在治疗60天内评估肿瘤生长；只有OVX、TAM及其与BROM的组合能够使肿瘤消退。这些结果支持了E2和催乳素在致癌作用促进阶段的重要作用。然而，对于已形成的肿瘤，生长变得更独立于激素影响，特别是不受催乳素缺乏的影响。我们得出结论，该模型似乎适合研究肿瘤生长逃避激素控制的潜在机制。
