Carcinogenesis, Vol 19, 383-386, Copyright © 1998 by Oxford University Press
HJ Thompson, J McGinley, K Rothhammer and M Singh
The experiments reported in this study were designed to examine the
question of whether a mammary epithelial cell's independence from hormonal
requirements is established at the time of carcinogenic initiation, or
whether the emergence of hormone independence is associated with the
process of tumor progression. A newly developed rat model of mammary
carcinogenesis was used in which the latency period to lesion detection is
very short and in which the frequencies of both pre- malignant and
malignant mammary lesions can be quantified. Two experiments were conducted
in Sprague-Dawley rats injected with 50 mg MNU/kg body wt at 21 days of
age. In the first experiment 47 animals were ovariectomized after the
detection of a mammary tumor of palpable size. Forty-six of the 47 tumors
assessed, all of which were subsequently classified as mammary gland
adenocarcinomas, regressed to <50% of their initial volume within 14
days of bilateral ovariectomy. However, both pre-malignant and malignant
mammary gland lesions were observed when animals were killed. In Experiment
2 a total of 60 rats were ovariectomized 7 days after MNU was injected. At
35 days post carcinogen ovariectomized animals had a higher incidence of
intraductal proliferations than sham-operated controls (P = 0.03); there
was no effect of ovariectomy on the incidence of ductal carcinoma in situ
or carcinoma. The multiplicity of intraductal proliferations was increased
by 58% in ovariectomized rats (P = 0.12), but the number of mammary
carcinoma per rat was reduced (3.8 vs. 1.57, P = 0.02). These data are
consistent with the hypotheses that the progression of pre-malignant to
malignant lesions is inhibited in the mammary gland by ovariectomy and that
the hormone independent phenotype can be conferred at the time of
carcinogenic initiation.
ARTICLES
Ovarian hormone dependence of pre-malignant and malignant mammary gland lesions induced in pre-pubertal rats by 1-methyl-1-nitrosourea
Division of Laboratory Research, AMC Cancer Research Center, Denver, CO 80214, USA. thompsonh@amc.org
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