Nakatani T, Roy G, Fujimoto N, Asahara T, Ito A
Department of Cancer Research, Research Institute for Radiation Biology, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8553, Japan.
Jpn J Cancer Res. 2001 Mar;92(3):249-56. doi: 10.1111/j.1349-7006.2001.tb01089.x.
The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3F(1) mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 mg / g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E(2) pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm (P < 0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and / or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors.
全球肝脏肿瘤的高发病率使得寻找化学预防剂成为当务之急。这种肿瘤似乎对激素有反应，因此激素干预可能有益。基于此，给12日龄的B6C3F(1)小鼠雌雄两性腹腔注射剂量为2.5 mg / g体重的二乙基亚硝胺（DEN），并观察32周（雄性）或36周（雌性）。在100%的雄性小鼠中观察到肝脏肿瘤，平均直径为2.72 mm，肿瘤数量为60.8个。这些小鼠在6周龄时进行睾丸切除，可将肿瘤发生率、数量和大小分别抑制至63%、5.6个和1.54 mm。通过每月间隔进一步植入雌二醇（E(2)）丸剂，这些参数分别降至26%、0.6个和0.61 mm。给经DEN处理的雄性小鼠施用一种促性腺激素阻断化学物质亮丙瑞林，可显著将肿瘤数量和大小分别降至18.3个和2.54 mm（与仅用DEN处理的小鼠相比，P < 0.01）。在雌性小鼠中，肝脏肿瘤的发生率明显低于雄性。然而，卵巢切除和/或补充睾酮显著增加了肝脏肿瘤的发生。一种抗雌激素药物托瑞米芬使肝脏肿瘤明显进一步减少。肿瘤组织中用溴脱氧尿苷检测的有丝分裂指数与肝脏肿瘤的发生情况平行。睾丸切除或施用亮丙瑞林可使血清睾酮水平显著降低。这些结果进一步证实肝脏肿瘤对睾酮有反应，通过手术睾丸切除或化学去势（即通过亮丙瑞林）进行激素干预可大幅预防肝脏肿瘤的出现。
