Thun-Battersby S, Mevissen M, Löscher W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine Hannover, Germany.
Cancer Res. 1999 Aug 1;59(15):3627-33.
We have shown previously (W. Löscher et al., Cancer Lett., 71: 75-81, 1993; M. Mevissen et al., Carcinogenesis (Lond.), 17: 903-910, 1996) that 50-Hz magnetic fields (MFs) of low [50 or 100 microTesla (T)] flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in female Sprague Dawley rats. In these previous experiments, groups of rats were given 20 mg of DMBA (four weekly gavage doses of 5 mg each) and were MF- or sham-exposed for 13 weeks. The objective of the present study was to examine whether the use of a lower dose of DMBA (10 instead of 20 mg per rat), MF exposure of the rats before DMBA injection, and the increase of the MF exposure period after DMBA application to 26 weeks enhance the effect of MF on tumor development and growth. A group 99 rats was exposed to a homogeneous, horizontally polarized 100-microT MF of 50-Hz for 24 h/day for 7 days/week; another group of 99 rats was sham-exposed under the same environmental conditions as the MF-exposed rats. The exposure chambers were identical for MF-exposed and sham-exposed animals. The age of the rats was 45-49 days at the onset of exposure; duration of MF or sham exposure was 27 weeks. DMBA was administered p.o. at a dose of 10 mg/rat after 1 week of MF or sham exposure. The animals were palpated once weekly from week 6 onwards to assess the development of mammary tumors. At the end of the exposure period, the animals were killed for the determination of number and volume and histological verification of mammary tumors. All of the recordings were done in a blinded fashion; i.e., the investigators were not aware which animals were MF- or sham-exposed. Mammary tumor development and growth was significantly enhanced by MF exposure, the most marked effect on tumor incidence (190% above sham control) being observed 13 weeks after DMBA administration. At the time of necropsy, i.e., 26 weeks after DMBA administration, the incidence of histologically verified mammary tumors was 50.5% in controls and 64.7% in MF-exposed rats, the difference being statistically significant. More marked intergroup differences were recorded when tumor incidence was separately evaluated for each of the six mammary complexes, the most pronounced MF effect on tumor incidence being seen in the cranial thoracic complex. The data substantiate that, at least under the experimental conditions used in our laboratory, 50-Hz, 100-microT MF exposure significantly facilitates the development and growth of mammary tumors in the DMBA rat model of breast cancer.
我们之前已表明（W. Löscher等人，《癌症通讯》，71: 75 - 81，1993年；M. Mevissen等人，《癌变（伦敦）》，17: 903 - 910，1996年），低通量密度[50或100微特斯拉（T）]的50赫兹磁场（MFs）可增强雌性斯普拉格 - 道利大鼠乳腺癌7,12 - 二甲基苯并[a]蒽（DMBA）模型中乳腺肿瘤的发生和生长。在这些之前的实验中，给大鼠分组给予20毫克DMBA（每周4次灌胃剂量，每次5毫克），并进行13周的MF暴露或假暴露。本研究的目的是检验使用较低剂量的DMBA（每只大鼠10毫克而非20毫克）、在注射DMBA前对大鼠进行MF暴露以及在应用DMBA后将MF暴露时间延长至26周是否会增强MF对肿瘤发生和生长的影响。一组99只大鼠每天24小时、每周7天暴露于50赫兹的100微特斯拉均匀水平极化MF；另一组99只大鼠在与MF暴露大鼠相同的环境条件下进行假暴露。MF暴露和假暴露动物的暴露室相同。暴露开始时大鼠年龄为45 - 49天；MF或假暴露持续时间为27周。在MF或假暴露1周后，以10毫克/大鼠的剂量经口给予DMBA。从第6周起每周对动物进行一次触诊，以评估乳腺肿瘤的发生情况。在暴露期结束时，处死动物以确定乳腺肿瘤的数量、体积并进行组织学验证。所有记录均以盲法进行；即，研究人员不知道哪些动物是MF暴露组或假暴露组。MF暴露显著增强了乳腺肿瘤的发生和生长，在给予DMBA后13周观察到对肿瘤发生率的影响最为显著（比假对照组高190%）。在尸检时，即给予DMBA后26周，组织学验证的乳腺肿瘤发生率在对照组中为50.5%，在MF暴露大鼠中为64.7%，差异具有统计学意义。当分别评估六个乳腺复合体各自的肿瘤发生率时，记录到更明显的组间差异，MF对肿瘤发生率的最显著影响见于颅胸复合体。数据证实，至少在我们实验室使用的实验条件下，50赫兹、100微特斯拉的MF暴露显著促进了DMBA大鼠乳腺癌模型中乳腺肿瘤的发生和生长。
