Thompson H J, McGinley J N, Rothhammer K, Singh M
Division of Laboratory Research, AMC Cancer Research Center, Lakewood, CO 80214, USA.
Carcinogenesis. 1995 Oct;16(10):2407-11. doi: 10.1093/carcin/16.10.2407.
While most data in the literature indicate that chemically-induced mammary carcinogenesis in the rat proceeds through morphologically identifiable stages, little quantitative data exist on the frequency of their occurrence. A carcinogen induction protocol is reported that defines conditions under which approximately 38% of detectable lesions in the abdominal-inguinal mammary glands were histologically classified as either intraductal proliferations or ductal carcinoma in situ. The remainder of the lesions were classified as carcinomas. This response was observed in a group of 30 female Sprague-Dawley rats injected i.p. with 50 mg 1-methyl-1-nitrosourea (MNU)/kg body wt at 21 days of age. The experiment was terminated 35 days following carcinogen administration. The methods used to prepare whole mounts and to identify, excise and process lesions in the whole mounts to permit histological classification are described in detail. This carcinogenesis protocol also induced a significant palpable tumor response. The first palpable tumor, histologically classified as an adenocarcinoma, was observed 30 days post carcinogen administration. When the experiment was terminated (35 days post MNU), the cumulative incidence of palpable carcinomas was 60%. The rapidity of the carcinogenic response was remarkable. Unlike the i.v. administration of 7,12-dimethylbenz[a]anthracene (DMBA) to rats of this age, MNU injection resulted in > 99% incidence of palpable mammary gland tumors that were malignant. The data reported in this paper confirm and support the pathogenetic pathway described for the induction of mammary tumors in the rat by DMBA. The induction of mammary carcinogenesis in immature animals described in this paper may be of value in the investigation of early morphologically identifiable stages of this disease process as well as providing an extremely rapid method for tumor induction.
虽然文献中的大多数数据表明，化学诱导的大鼠乳腺癌发生过程会经历形态学上可识别的阶段，但关于这些阶段发生频率的定量数据却很少。本文报道了一种致癌物诱导方案，该方案定义了一些条件，在这些条件下，腹腹股沟乳腺中约38%的可检测病变在组织学上被分类为导管内增生或原位导管癌。其余病变被分类为癌。在一组30只雌性Sprague-Dawley大鼠中观察到了这种反应，这些大鼠在21日龄时经腹腔注射50 mg 1-甲基-1-亚硝基脲（MNU）/kg体重。在给予致癌物35天后终止实验。详细描述了用于制备全组织切片以及识别、切除和处理全组织切片中的病变以进行组织学分类的方法。这种致癌方案还诱导了显著的可触及肿瘤反应。在给予致癌物30天后观察到第一个可触及的肿瘤，组织学上分类为腺癌。当实验终止时（MNU给药后35天），可触及癌的累积发生率为60%。致癌反应的速度非常快。与给这个年龄段的大鼠静脉注射7,12-二甲基苯并[a]蒽（DMBA）不同，注射MNU导致可触及的乳腺肿瘤中有超过99%是恶性的。本文报道的数据证实并支持了DMBA诱导大鼠乳腺肿瘤的发病机制途径。本文所述的未成熟动物乳腺致癌作用的诱导，可能在研究该疾病过程早期形态学上可识别的阶段以及提供一种极其快速的肿瘤诱导方法方面具有价值。
