Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats.
In line with the possible relationship between electric power and breast cancer risk as well as the underlying "melatonin hypothesis," we have shown previously (Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that 50-Hz magnetic fields (MFs) of low (100 microTesla) flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene model of breast cancer in female Sprague Dawley rats. On the basis of the melatonin hypothesis and previous observations of induction of ornithine decarboxylase in response to MF, we proposed that the effect of MF exposure on mammary carcinogenesis is related to enhanced proliferation of the mammary epithelium. The objective of the present study was to directly assess this proposal by the use of proliferation markers. Female Sprague Dawley rats were MF or sham exposed for 2 weeks at a flux density of 100 microTesla. Proliferation of epithelial cells in the mammary tissue and adjacent skin was examined by in vivo labeling of proliferating cells with bromodeoxyuridine (BrdUrd) and in situ labeling of the nuclear proliferation-associated Ki-67 protein by the antibody MIB-5. Furthermore, melatonin levels were determined after MF or sham exposure in the pineal gland and directly in the mammary tissue. In additional experiments, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate was used for comparison with the effects of MF exposure. MF exposure significantly enhanced BrdUrd and Ki-67 labeling in the mammary epithelium, indicating a marked increase in cell proliferation. The most pronounced effect on proliferation was seen in the cranial thoracic (or cervical) mammary complexes, in which we previously had seen the most marked effects of MF exposure on mammary carcinogenesis. In contrast to the melatonin hypothesis, melatonin levels in pineal or mammary glands were not affected by MF exposure. Topical application of 12-O-tetradecanoylphorbol-13-acetate increased BrdUrd and Ki-67 labeling in epithelial cells of the skin, particularly in hair follicles, but not in the mammary tissue. The data demonstrate that MF exposure results in an increased proliferative activity of the mammary epithelium, which is a likely explanation for the cocarcinogenic or tumor promoting effects of MF exposure observed previously by us in the 7,12-dimethylbenz(a)anthracene model of breast cancer.
Fedrowitz
Maren
M
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, D-30559 Hannover, Germany.
Westermann
Jürgen
J
Löscher
Wolfgang
W
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D019394:Ki-67 Antigen / Q000032:analysis; D008280:Magnetics / Q000009:adverse effects*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects*; D008550:Melatonin / Q000032:analysis*; D010870:Pineal Gland / Q000737:chemistry / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019394:Ki-67 Antigen; D015127:9,10-Dimethyl-1,2-benzanthracene; D001973:Bromodeoxyuridine; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate