Murin Susan, Pinkerton Kent E, Hubbard Neil E, Erickson Kent
Division of Pulmonary and Critical Care Medicine, University of California Davis School of Medicine, Davis, CA, USA.
Chest. 2004 Apr;125(4):1467-71. doi: 10.1378/chest.125.4.1467.
Women who smoke have a higher rate of fatal breast cancer than nonsmoking women. An association between smoking and pulmonary metastases from breast cancer has been suggested by epidemiologic studies.
To examine the relationship between exposure to cigarette smoke and pulmonary metastasis in a murine model of metastatic mammary cancer.
Prospective, randomized study.
Animal research laboratory.
Female sexually mature BALB/cAnN mice.
Mice were randomly divided into experimental and control groups. Experimental animals were exposed to cigarette smoke in specialized exposure chambers, at concentrations chosen to approximate active cigarette smoking. Control animals were exposed to filtered air. One week after the initiation of exposures, mouse mammary tumor cells (tumor cell line 4526) were injected into the tail veins of experimental animals at one of three concentrations (50,000, 100,000, or 150,000 cells per 100 micro L). Three weeks later, the mice were killed, and pulmonary metastases were counted and measured.
The mean metastatic burden in the lungs was consistently greater for smoke-exposed animals at each concentration of cells injected (at 50,000 cells per 100 micro L, 9.8 vs 4.8 micro m(3), respectively [p < 0.01]; at 100,000 cells per 100 micro L, 34.5 vs 17.4 micro m(3), respectively [p < 0.10]; and at 150,000 cells per 100 micro L, 54.0 vs 31.5 micro m(3), respectively [p < 0.05]). This was largely attributable to a significant increase in the number of metastatic nodules per animal (at 50,000 cells per 100 micro L, 8.7 vs 4.8, respectively [p < 0.001]; at 100,000 cells per 100 micro L, 24.3 vs 14.0, respectively [p > 0.10]; and at 150,000 cells per 100 micro L, 42.0 vs 20.1, respectively [p < 0.02]) rather than to a change in nodule size.
Cigarette smoke exposure is associated with an increase in the total pulmonary metastatic burden in this murine model of metastatic mammary cell cancer. This study provides experimental support for an adverse effect of smoking on the metastatic process and suggests a possible mechanism for smokers' increased breast cancer mortality.
吸烟女性患致命性乳腺癌的几率高于不吸烟女性。流行病学研究表明吸烟与乳腺癌肺转移之间存在关联。
在转移性乳腺癌小鼠模型中研究接触香烟烟雾与肺转移之间的关系。
前瞻性随机研究。
动物研究实验室。
性成熟的雌性BALB/cAnN小鼠。
将小鼠随机分为实验组和对照组。实验组动物在专门的暴露舱中接触香烟烟雾，浓度设定为接近实际主动吸烟的水平。对照组动物接触过滤空气。暴露开始一周后，将小鼠乳腺肿瘤细胞（肿瘤细胞系4526）以三种浓度之一（每100微升50000、100000或150000个细胞）注入实验组动物的尾静脉。三周后，处死小鼠，对肺转移灶进行计数和测量。
在每个注射细胞浓度下，接触烟雾的动物肺部的平均转移负荷始终更高（每100微升50000个细胞时，分别为9.8立方毫米和4.8立方毫米 [p < 0.01]；每100微升100000个细胞时，分别为34.5立方毫米和17.4立方毫米 [p < 0.10]；每100微升150000个细胞时，分别为54.0立方毫米和31.5立方毫米 [p < 0.05]）。这主要归因于每只动物转移结节数量的显著增加（每100微升50000个细胞时，分别为8.7个和4.8个 [p < 0.001]；每100微升100000个细胞时，分别为24.3个和14.0个 [p > 0.10]；每100微升150000个细胞时，分别为42.0个和20.1个 [p < 0.02]），而非结节大小的变化。
在这个转移性乳腺细胞癌小鼠模型中，接触香烟烟雾与肺部总转移负荷增加有关。本研究为吸烟对转移过程的不利影响提供了实验支持，并提示了吸烟者乳腺癌死亡率增加的一种可能机制。
