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极低频电磁场的促癌作用是否需要与致癌物反复长期相互作用?使用二甲基苯并蒽大鼠乳腺癌模型的阳性研究特征。

Do cocarcinogenic effects of ELF electromagnetic fields require repeated long-term interaction with carcinogens? Characteristics of positive studies using the DMBA breast cancer model in rats.

作者信息

Löscher W

机构信息

Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany.

出版信息

Bioelectromagnetics. 2001 Dec;22(8):603-14. doi: 10.1002/bem.90.

DOI:10.1002/bem.90
PMID:11748679
Abstract

The carcinogenic or cocarcinogenic potential of extremely low frequency (ELF; 50 or 60 Hz) magnetic fields (MFs) has been evaluated worldwide in diverse animal model systems. Though most results have been negative, weakly positive or equivocal results have been reported in several cancer models, including the rat DMBA (7,12-dimethylbenz[a]anthracene) model of mammary cancer. Based on the experimental conditions used in studies in which cocarcinogenic effects of ELF MF were found, it was recently proposed that MF exposure may potentiate the effects of known carcinogens only when the animals are exposed to both MF and carcinogen during an extended period of tumor development, i.e., when the carcinogen is given repeatedly during MF exposure. This review summarizes a series of experiments from our group, showing cocarcinogenic MF effects in the DMBA breast cancer model in rats, to test whether the above proposal is confirmed by existing data. Flux densities of 50 or 100 microT significantly increased the growth of mammary tumors, independent of whether DMBA was given in a single administration or repeatedly over a prolonged period. Thus, these data do not substantiate the hypothesis requiring repeated doses of DMBA during MF exposure. Instead, several other aspects of study design and experimental factors are identified that seem to be critical for the detection of cocarcinogenic effects of MF exposure in the rat DMBA mammary cancer model. These include the rat subline used, the dose of DMBA, the duration of MF exposure, the flux density, the background (sham control) tumor incidence, and the location of mammary tumors in the mammary gland complex. These and other experimental aspects may explain why some laboratories did not detect cocarcinogenic MF effects in the DMBA model. We hope that direct comparison of MF bioeffects in different rat sublines and further evaluation of other experimental differences between studies on MF exposure in the DMBA model will eventually determine which genetic and environmental factors are critical for potential carcinogenic or cocarcinogenic effects of ELF MF exposure.

摘要

全世界已在多种动物模型系统中评估了极低频(ELF;50或60赫兹)磁场(MF)的致癌或促癌潜力。尽管大多数结果为阴性,但在包括大鼠乳腺癌的二甲基苯并蒽(DMBA,7,12 - 二甲基苯并[a]蒽)模型在内的几种癌症模型中报告了弱阳性或模棱两可的结果。基于发现ELF MF促癌作用的研究中所使用的实验条件,最近有人提出,仅当动物在肿瘤发展的较长时期内同时暴露于MF和致癌物时,即当在MF暴露期间反复给予致癌物时,MF暴露才可能增强已知致癌物的作用。本综述总结了我们小组的一系列实验,这些实验显示了大鼠DMBA乳腺癌模型中的MF促癌作用,以检验上述提议是否得到现有数据的证实。50或100微特斯拉的磁通密度显著增加了乳腺肿瘤的生长,无论DMBA是单次给药还是在较长时期内反复给药。因此,这些数据并未证实需要在MF暴露期间反复给予DMBA的假设。相反,确定了研究设计和实验因素的其他几个方面,这些方面似乎对于在大鼠DMBA乳腺癌模型中检测MF暴露的促癌作用至关重要。这些包括所使用的大鼠亚系、DMBA的剂量、MF暴露的持续时间、磁通密度、背景(假对照)肿瘤发生率以及乳腺肿瘤在乳腺复合体中的位置。这些以及其他实验方面可能解释了为什么一些实验室在DMBA模型中未检测到MF促癌作用。我们希望直接比较不同大鼠亚系中的MF生物效应,并进一步评估DMBA模型中MF暴露研究之间的其他实验差异,最终将确定哪些遗传和环境因素对于ELF MF暴露的潜在致癌或促癌作用至关重要。

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