Takahashi H, Uemura Y, Nakao I, Tsubura A
Department of Pathology, Kansai Medical University, Osaka, Japan.
Cancer Lett. 1995 May 25;92(1):105-11. doi: 10.1016/0304-3835(95)03761-k.
The effectiveness of the direct application of crystalline N-methyl-N-nitrosourea (MNU) onto the mammary gland was compared with the systemic intraperitoneal (i.p.) administration method for the induction of mammary carcinomas in female Sprague-Dawley (S-D) rats. The effectiveness was also tested in genetically resistant female Copenhagen (Cop) rats. The 10 mg crystalline MNU was dusted directly onto the right-inguinal mammary gland, or 50 mg/kg body weight MNU solution was given i.p. at 50 days of age. Animals were palpated for tumor detection twice weekly and killed when the tumor reached 1-2 cm in diameter or were necropsied 30 weeks after carcinogen treatment. In S-D rats, all of the 78 tumors produced by dusting were adenocarcinomas. By contrast, 40 tumors produced i.p. were adenocarcinomas, 1 was fibroadenoma, and 5 were lactating adenomas. The cumulative incidence of mammary carcinoma was high in the dusting and the i.p. groups (12/12; 100% and 11/13; 84%, respectively). However, the dusting groups showed a high number of carcinoma per rats (6.5 vs. 3.6; P < 0.01) and short cancer latency (13.8 weeks v.s. 28.1 weeks; P < 0.001) than the i.p. groups. In Cop rats, although low (4/11; 36%), adenocarcinomas were developed by the dusting method. In both strains, adenocarcinomas displayed various degrees of differentiation but no evidence was found for metastasis. For MNU-administration, the direct dusting technique is an effective method and offers added advantages of ease for the induction of mammary carcinomas in rats.
将结晶状的N-甲基-N-亚硝基脲（MNU）直接应用于乳腺的效果，与通过腹腔内（i.p.）全身给药法诱导雌性斯普拉格-道利（S-D）大鼠发生乳腺癌的效果进行了比较。还在具有遗传抗性的雌性哥本哈根（Cop）大鼠中测试了该效果。在50日龄时，将10mg结晶状MNU直接撒在右腹股沟乳腺上，或腹腔注射50mg/kg体重的MNU溶液。每周对动物进行两次触诊以检测肿瘤，当肿瘤直径达到1-2cm时将动物处死，或者在致癌物处理后30周进行尸检。在S-D大鼠中，通过撒粉产生的78个肿瘤均为腺癌。相比之下，腹腔注射产生的40个肿瘤中，40个为腺癌，1个为纤维腺瘤，5个为泌乳性腺瘤。乳腺癌的累积发生率在撒粉组和腹腔注射组中都很高（分别为12/12；100%和11/13；84%）。然而，撒粉组每只大鼠的癌数量较多（6.5比3.6；P<0.01），且癌症潜伏期较短（13.8周对28.1周；P<0.001），比腹腔注射组短。在Cop大鼠中，虽然通过撒粉法发生腺癌的比例较低（4/11；36%）。在两种品系中，腺癌均表现出不同程度的分化，但未发现转移迹象。对于MNU给药，直接撒粉技术是一种有效的方法，并且在诱导大鼠乳腺癌方面具有操作简便的额外优势。
