Braun R J, Pezzuto J M, Anderson C H, Beattie C W
Division of Surgical Oncology, University of Illinois College of Medicine, Chicago 60612.
Cancer Lett. 1989 Dec;48(3):205-11. doi: 10.1016/0304-3835(89)90119-5.
The relationship between mammary carcinoma growth, ovariectomy-induced regression and estrogen receptor status were determined in Sprague-Dawley rats with 5-day estrous cycles after injection of N-methyl-N-nitrosourea (NMU) on metestrus (ME), diestrus-1 (DE-1), proestrus (PE) or estrus (E). Rats exposed to NMU on PE had a shorter tumor latency than those injected on ME and E, as well as more carcinomas per rat than those exposed on ME and DE-1. Mammary carcinomas grew faster in rats injected on ME (doubling time, 6.4 days) and DE-1 (6.9 days) compared with PE (15.2 days) and E (16.3 days). Tumor regression was also significantly faster in rats injected on ME (time to 50% vol., 5.5 days) and DE-1 (5.3 days) compared with PE (8.2 days) and E (8.5 days) following bilateral-ovariectomy during log phase growth. Significantly, total nuclear estrogen receptor (ERN) content was increased in carcinomas from rats injected on PE compared with DE-1 (70.8 +/- 11.3 vs. 32.9 +/- 7.3 fm/mg DNA) (P less than 0.05) and DE-1 and ME combined (P less than 0.01). These observations generalize the concept that estrous cycle stage at the time of NMU injection alters subsequent mammary carcinoma biology, and represents the first experimental evidence that slower growing and responding estrogen receptor positive rat mammary carcinomas may be associated with an increase in circulating estrogen prior to carcinogen exposure.
在动情后期（ME）、动情间期-1（DE-1）、动情前期（PE）或动情期（E）给处于5天发情周期的斯普拉格-道利大鼠注射N-甲基-N-亚硝基脲（NMU），以确定乳腺癌生长、卵巢切除诱导的消退与雌激素受体状态之间的关系。在PE期接受NMU注射的大鼠肿瘤潜伏期比在ME期和E期注射的大鼠短，并且每只大鼠的癌灶数量比在ME期和DE-1期接受注射的大鼠多。与在PE期（15.2天）和E期（16.3天）注射的大鼠相比，在ME期（倍增时间为6.4天）和DE-1期（6.9天）注射的大鼠乳腺癌生长更快。在对数生长期进行双侧卵巢切除后，与PE期（8.2天）和E期（8.5天）相比，在ME期（达到50%体积的时间为5.5天）和DE-1期（5.3天）注射的大鼠肿瘤消退也明显更快。值得注意的是，与DE-1期（70.8±11.3对32.9±7.3 fm/mg DNA）（P<0.05）以及DE-1期和ME期合并组（P<0.01）相比，在PE期注射的大鼠癌灶中总核雌激素受体（ERN）含量增加。这些观察结果概括了NMU注射时的发情周期阶段会改变后续乳腺癌生物学特性这一概念，并且代表了首个实验证据，即生长较慢且对雌激素受体阳性的大鼠乳腺癌可能与致癌物暴露前循环雌激素增加有关。
