Estrous cycle status alters N-methyl-N-nitrosourea (NMU)-induced rat mammary tumor growth and regression.
Estrous cycle status alters N-methyl-N-nitrosourea (NMU)-induced rat mammary tumor growth and regression.
复制标题
发情周期状态改变 N-甲基-N-亚硝基脲 (NMU) 诱导的大鼠乳腺肿瘤生长和消退。
DOI：
10.1016/0304-3835(89)90119-5
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发表时间：
1989
期刊：
影响因子：
9.7
通讯作者：
Beattie,CW
中科院分区：
文献类型：
--
作者：
Braun,RJ;Pezzuto,JM;Anderson,CH;Beattie,CW
在发情周期为 5 天的 Sprague-Dawley 大鼠中，在发情后期 (ME)、发情间期 1 (DE-1)、发情前期 (PE) 或发情期 (E) 注射 N-甲基-N-亚硝基脲 (NMU) 后，确定乳腺癌生长、卵巢切除诱导的消退和雌激素受体状态之间的关系。在 PE 上暴露于 NMU 的大鼠比在 ME 和 E 上注射的大鼠具有更短的肿瘤潜伏期，并且每只大鼠比在 ME 和 DE-1 上注射的大鼠有更多的癌症。与PE（15.2天）和E（16.3天）相比，注射ME（倍增时间，6.4天）和DE-1（6.9天）的大鼠的乳腺癌生长更快。在对数生长期双侧卵巢切除术后，与 PE（8.2 天）和 E（8.5 天）相比，注射 ME（达到 50% 体积的时间，5.5 天）和 DE-1（5.3 天）的大鼠的肿瘤消退也明显更快。显着的是，与 DE-1 相比，注射 PE 的大鼠的癌症中总核雌激素受体 (ERN) 含量增加（70.8 ± 11.3 vs. 32.9 ± 7.3 fm/mg DNA）（P < 0.05）以及 DE-1 和 ME 组合（P < 0.01）。这些观察概括了这样一个概念，即注射 NMU 时的动情周期阶段会改变随后的乳腺癌生物学，并且代表了第一个实验证据，表明生长缓慢和响应雌激素受体阳性的大鼠乳腺癌可能与致癌物暴露之前循环雌激素的增加有关。
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 < 0.05) and DE-1 and ME combined (P < 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.