Mevissen M, Häussler M, Löscher W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Bioelectromagnetics. 1999 Sep;20(6):338-46. doi: 10.1002/(sici)1521-186x(199909)20:6<338::aid-bem2>3.0.co;2-j.
In a series of experiments with the chemical carcinogen DMBA (7, 12-dimethyl[a]anthracene), we recently found that exposure of female Sprague-Dawley rats in 50 Hz magnetic fields (MF) in the microtesla range significantly facilitates the development and growth of mammary tumors. One possible explanation for this finding would be enhanced proliferation of breast epithelial stem cells by MF exposure, thereby increasing the sensitivity of these cells to chemical carcinogens. In line with this possibility, we previously determined that 50 Hz, 50 microT MF exposure induces increases in ornithine decarboxylase (ODC), i.e., a key enzyme in cell proliferation, in the mammary gland of female Sprague-Dawley rats. In the present study, we examined the time course of this effect, by using different periods of exposure to a 50 Hz, 100 microT MF. Furthermore, we determined ODC in different mammary complexes of the rat mammary gland to evaluate whether differences in response to MF exist over the anterior-posterior extension of this organ. Exposure of young female Sprague-Dawley rats induced marked increases in ODC in the mammary gland that were similar to ODC increases seen in "positive control" experiments with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). However, this effect of MF critically depended on the duration of MF exposure, with no effect, or at least no consistent effect, for short (<1 week) or long (8 weeks and above) exposure periods, but a robust and reproducible enhancing effect on ODC activity after 2 weeks of exposure. Furthermore, we found that the effect of MF exposure depends on the part of the mammary complexes examined, the cranial thoracic (or cervical) complexes being particularly sensitive to ODC alterations in response to MF. This is in line with recent DMBA experiments of our group in which MF-induced increases in tumor development and growth were predominantly seen in this large cranial/cervical part of the mammary gland. The most likely explanation for the observed ODC changes after MF exposure is the "melatonin hypothesis," although other cellular and molecular effects of MF might be involved as well.
在一系列使用化学致癌物DMBA（7,12 - 二甲基[a]蒽）的实验中，我们最近发现，将雌性斯普拉格 - 道利大鼠暴露于微特斯拉范围内的50Hz磁场（MF）中，会显著促进乳腺肿瘤的发生和生长。对这一发现的一种可能解释是，MF暴露会增强乳腺上皮干细胞的增殖，从而增加这些细胞对化学致癌物的敏感性。与此可能性相符的是，我们之前确定，暴露于50Hz、50微特斯拉的MF会导致雌性斯普拉格 - 道利大鼠乳腺中鸟氨酸脱羧酶（ODC）增加，ODC是细胞增殖中的一种关键酶。在本研究中，我们通过使用不同时长暴露于50Hz、100微特斯拉MF的方式，研究了这种效应的时间进程。此外，我们测定了大鼠乳腺不同乳腺复合体中的ODC，以评估在该器官的前后延伸范围内，对MF的反应是否存在差异。暴露于年轻雌性斯普拉格 - 道利大鼠会导致乳腺中ODC显著增加，这与使用肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）的“阳性对照”实验中观察到的ODC增加相似。然而，MF的这种效应严重依赖于MF暴露的持续时间，短期（<1周）或长期（8周及以上）暴露没有效果，或者至少没有一致的效果，但暴露2周后对ODC活性有强烈且可重复的增强作用。此外，我们发现MF暴露的效应取决于所检查的乳腺复合体部分，颅胸部（或颈部）复合体对MF引起的ODC变化特别敏感。这与我们小组最近的DMBA实验一致，在该实验中，MF诱导的肿瘤发生和生长增加主要出现在乳腺的这个大的颅部/颈部区域。MF暴露后观察到的ODC变化最可能的解释是“褪黑素假说”，尽管MF的其他细胞和分子效应可能也参与其中。
