ABSTRACT: Magnetic Field Exposure Increases Cell Proliferation
but Does Not Affect Melatonin Levels in the Mammary Gland of
Female Sprague Dawley Rats
[03/13/2002; Cancer Research]
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 micro-Tesla) 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.
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.
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
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.
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