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磁场暴露对斯普拉格-道利大鼠两个亚系中7,12-二甲基苯并(a)蒽诱导的乳腺癌发生影响的显著差异。

Significant differences in the effects of magnetic field exposure on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of Sprague-Dawley rats.

作者信息

Fedrowitz Maren, Kamino Kenji, Löscher Wolfgang

机构信息

Department of Pharmacology, Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.

出版信息

Cancer Res. 2004 Jan 1;64(1):243-51. doi: 10.1158/0008-5472.can-03-2808.

Abstract

We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356-1363, 2002), which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. However, in contrast with our data, in a similar study conducted by Battelle in the United States, no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615-1620, 1999). Probably the most important difference between our and the Battelle studies was the use of different substrains of SD rats; the United States rats were much more susceptible to DMBA than the rats used in our studies. This prompted us to compare different substrains of SD outbred rats in our laboratory in respect to MF effects on cell proliferation in the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects on mammary tumor development and growth in the DMBA model. The SD substrain (termed "SD1") used in all of our previous studies was considered MF-sensitive and used for comparison with another substrain ("SD2") obtained from the same breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor development and growth in SD1 but not SD2 rats. These data indicate that the genetic background plays a pivotal role in effects of MF exposure. Different strains or substrains of rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.

摘要

我们之前已经表明(S. 图恩 - 巴特斯比等人,《癌症研究》,59: 3627 - 3633, 1999),在雌性斯普拉格 - 道利(SD)大鼠的7,12 - 二甲基苯并(a)蒽(DMBA)乳腺癌模型中,微特斯拉磁通密度的电力线频率(50赫兹)磁场(MFs)会促进乳腺肿瘤的发展和生长。我们还证明,暴露于MF会导致SD大鼠乳腺上皮细胞增殖活性增强(M. 费德罗维茨等人,《癌症研究》,62: 1356 - 1363, 2002),这可能是MF暴露在DMBA模型中具有促癌或肿瘤促进作用的一个解释。然而,与我们的数据相反,在美国巴特尔研究所进行的一项类似研究中,未发现MF暴露在SD大鼠的DMBA模型中有促癌或肿瘤促进作用的证据(L. E. 安德森等人,《癌变》,20: 1615 - 1620, 1999)。我们和巴特尔研究之间可能最重要的差异在于使用了不同亚系的SD大鼠;美国的大鼠比我们研究中使用的大鼠对DMBA更敏感。这促使我们在实验室中比较不同亚系的远交SD大鼠在MF对乳腺细胞增殖的影响、对DMBA诱导的乳腺癌的易感性以及MF对DMBA模型中乳腺肿瘤发展和生长的影响方面的差异。我们之前所有研究中使用的SD亚系(称为“SD1”)被认为对MF敏感,并用于与从同一饲养者处获得的另一个亚系(“SD2”)进行比较。与SD1大鼠相反,在SD2大鼠中,MF暴露后未检测到细胞增殖增强。MF暴露显著增加了SD1大鼠乳腺肿瘤的发展和生长,但对SD2大鼠没有影响。这些数据表明,遗传背景在MF暴露的影响中起关键作用。不同品系或亚系的大鼠可用于评估对MF暴露的促癌或肿瘤促进作用敏感性的潜在遗传因素。

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