HUGGINS C, BRIZIARELLI G, SUTTON H
J Exp Med. 1959 Jan 1;109(1):25-42. doi: 10.1084/jem.109.1.25.
A study was made of the optimal conditions for the induction of mammary cancer in the rat. 3-Methylcholanthrene was administered via the gastrointestinal tract, and a simple technique was worked out for inducing mammary cancer regularly and rapidly. Under conducive conditions, which were readily reproduced, multiple mammary carcinomas and these tumors only were induced in every rat in repeated experiments in 60 days or less. In the strain of animal employed in the present experiments, the rapid induction of mammary cancer proved to be a function of (a) dosage, (b) the timing of administration of the aromatic hydrocarbon, and (c) a favoring hormonal status of the recipient. Most of the established tumors were hormone-dependent because they diminished markedly in size after hormone withdrawal through ovariectomy or hypophysectomy. Similar regression of the tumors was frequently achieved by the administration of dihydrotestosterone. Shrinkage of the cancers was accompanied by atrophic changes. Experimental mammary tumors with these physiologic characteristics have not been recognized hitherto. The minority of mammary cancers continued to grow after ovariectomy; these are hormone-independent tumors and tumors of this sort had a characteristic cytologic appearance following modification of the endocrine state. The cell population of a single tumor was not always uniform in its response to appropriate hormonal modifications. In certain tumors in response to changes in the endocrine status of the host many of the cells underwent atrophy whilst other adjacent cells in the same tumor continued to grow so that the net result was a hormone-independent tumor. Hypophysectomy was the most effective method found to induce regression of mammary cancer in the present experiments.
对大鼠诱发乳腺癌的最佳条件进行了研究。通过胃肠道给予3-甲基胆蒽，并制定了一种简单的技术，可定期且快速地诱发乳腺癌。在易于重现的有利条件下，在60天或更短时间内的重复实验中，每只大鼠都诱发了多发性乳腺癌且只有这些肿瘤。在本实验所使用的动物品系中，乳腺癌的快速诱发证明是以下因素的作用：（a）剂量，（b）芳香烃的给药时间，以及（c）受体有利的激素状态。大多数已形成的肿瘤依赖激素，因为通过卵巢切除或垂体切除去除激素后，它们的大小会明显减小。通过给予二氢睾酮也经常能使肿瘤出现类似的消退。肿瘤缩小伴随着萎缩性变化。迄今为止尚未认识到具有这些生理特征的实验性乳腺肿瘤。少数乳腺癌在卵巢切除后继续生长；这些是激素非依赖性肿瘤，并且这类肿瘤在内分泌状态改变后具有特征性的细胞学表现。单个肿瘤的细胞群体对适当的激素改变的反应并不总是一致的。在某些肿瘤中，响应宿主内分泌状态的变化，许多细胞发生萎缩，而同一肿瘤中其他相邻细胞继续生长，因此最终结果是形成了激素非依赖性肿瘤。在本实验中，垂体切除是发现的诱导乳腺癌消退的最有效方法。
