Hormonal Influences on Mammary Tumors of the Rat

Huggins, Charles; Torralba, Yolanda; Mainzer, K.

doi:10.1084/jem.104.4.525

Cited by 32 publications

(8 citation statements)

References 14 publications

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“…The benign mammary fibroadenoma studied in the present work grows to a considerable size within 50 days in normal adult female rats whereas its growth is slight after the ovaries have been removed; the retarding effect of ovariectomy upon the growth of a similar tumor has been described earlier (2). The growth of the tumor is enhanced profoundly in ovariectomized rats by the administration of phenolic estrogens in critical quantities, or progesterone (1). In hypophysectomized rats (1) the tumor grows indolently but after some weeks active growth commences despite the absence of growth-promoting hormones as determined by absence of growth in the atrophic tissues of the host--a sensitive biological test.…”

Section: (From the Ben May Laboratory For Cancer Research Of The Univsupporting

confidence: 66%

Hormonal Influences on Mammary Tumors of the Rat

Huggins

Mainzer

1957

The Journal of Experimental Medicine

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It was found in the experiments to be described that many steroids in the androstane series profoundly retard the growth of a transplanted benign mammary tumor in adult intact female rats. This paper is concerned with the relationship of the molecular structure of these steroids to their inhibitory effects on the tumor and with mechanisms involved in the depression of neoplastic growth by these agents. A quantitative relationship was found to exist between the dosage of the steroid administered and the extent of the restraint of the tumor which ensued. In the variations of its growth rate in response to hormonal modifications the benign tumor of the rat resembles some human mammary carcinomas, and in this regard it is a serviceable laboratory model that is unique at the present time. The growth of the transplanted tumor is accelerated or retarded by hormones which already have been found through clinical practice to have like effects on carcinoma of the breast of the human being. The availability of quantitative methods of study of a hormone-responsive experimental tumors expands the scope of investigation of mammary neoplasms.The mammary fibroadenoma employed in the experiments has two outstanding characteristics. It is a neoplasm. Secondly, the tumor possesses some of the responsiveness to hormones which is characteristic of normal mammary epithelium of the rat in so far as its growth rate is profoundly altered by the administration or withdrawal of appropriate hormones. With respect to the promotion of growth by steroid and protein hormones, it was shown earlier (1) that there are many similarities in the reactivity of both the transplanted

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Section: (From the Ben May Laboratory For Cancer Research Of The Univsupporting

confidence: 66%

Hormonal Influences on Mammary Tumors of the Rat

Huggins

Mainzer

1957

The Journal of Experimental Medicine

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“…in the two groups but the content of alkaline phosphatase was considerably lower in the mammary glands of the carcinogen-fed rats. A consequence of ovariectomy in the rat is a decreased content of alkaline phosphatase in the mammary glands accompanied by atrophy of epithelium (23). In the carcinogen-treated rats alkaline phosphatase content of the breast was decreased but the mammary epithelium was not atrophic; to the contrary, a moderately increased epithelial proliferation was present (Fig.…”

Section: Influence Of Hormonal Status On the Development Of Mammary Cmentioning

confidence: 91%

Rapid Induction of Mammary Carcinoma in the Rat and the Influence of Hormones on the Tumors

Huggins

Briziarelli

Sutton

1959

The Journal of Experimental Medicine

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336

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It has been known for some years that certain aromatic hydrocarbons induce mammary tumors in some species of rodents. This paper is concerned with the conditions required for the rapid and invariable induction of mammary cancer in the rat by administering 3-methylcholanthrene v/a the gastro-intestinal tract and with some of the functional characteristics of the tumors which were evoked. During the experiments, a novel observation was made when it was found that the majority of the induced carcinomas of the breast are hormonedependent, since they regress when the supporting internal secretions are removed. Whilst the concept of hormone dependence has been established in human mammary cancer, this property has not been recognized previously in mammary carcinomas of laboratory animals.Tumors develop preferentially in the mammary gland of certain strains of mice and rats following the remote administration of some aromatic compounds; the local application of such carcinogens to the region of the mammary gland is unnecessary for the production of breast tumors. This effect was discovered by Lacassagne (I) who found that the administration of estrone induced mammary cancer in mice of the R I I I strain.But mammary cancer can be evoked by compounds without hormonal activity; amongst these carcinogens are 3-methylcholanthrene (2), 2-acetylaminofluorene (2-AAF) 1 (3, 4), and 7,12-dimethylbenz-a-anthracene (DMBA) ~ (5). This remarkable activity of non-estrogenic carcinogens in inducing cancers of the mammary glands was first observed by Maisin and Coolen (2) who painted the skin of mice with 3-methylcholanthrene and found that, in addition to production of skin cancer, carcinoma of the mammary gland developed in high incidence. Mammary tumors have also been elicited with great frequency after the repeated instillation of 3-methylcholanthrene in the mouth (6), nares (7), or stomach (8) of the mouse or rat. Repeated intravenous injections of DMBA evoked similar tumors (5).

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“…Alternatively, naltrexone may indirectly decrease oestrogen or progesterone levels. Research has shown that the growth of transplanted mammary fibroadenomas is retarded by ovariectomy in rats, with the effect strengthened when combined with an adrenalectomy [50]. Similarly in ovarectomised rats, the growth of tumours could be stimulated using phenolic oestrogens, and even more so when combined with progesterone [50].…”

Section: Discussionmentioning

confidence: 99%

“…Research has shown that the growth of transplanted mammary fibroadenomas is retarded by ovariectomy in rats, with the effect strengthened when combined with an adrenalectomy [50]. Similarly in ovarectomised rats, the growth of tumours could be stimulated using phenolic oestrogens, and even more so when combined with progesterone [50]. Abou-Issa and Tejwani found that DMBA induced tumours that responded to naltrexone had both estrogen and progesterone receptors while unresponsive tumours were negative for both receptor types [49].…”

Section: Discussionmentioning

confidence: 99%

The Occurrence of Spontaneous Lymphomas but Not Adenomas or Sarcomas in Rats Treated With Sustained Release Naltrexone

Kelty¹

2012

Clin Exp Pharmacol

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Naltrexone has been observed to have both a stimulatory and inhibitory effect on the development of tumours in rodents, potentially mediated by changes to the neuroendocrine system as a result of blockade of the opiate receptors, with the period of blockade and the tumour type thought to be influential. This study examined the occurrence of spontaneous tumours in rats treated with a sustained release naltrexone preparation. Materials and methods: 27 male and 27 female rats were randomized into three equal treatment groups (A, B and C). Rats in group A were implanted with a single naltrexone implant tablet, rats in group B were implanted with a single polymer implant tablet (placebo) and rats in group C underwent a sham procedure (control). Three different groups of spontaneous tumours were observed; lymphomas, adenomas and sarcomas. Lymphomas (4 tumours/3 rats) were observed solely in naltrexone treated rats, while adenomas (9 tumours/5 rats) and sarcomas (4 tumours/3 rats) were only observed in the placebo and the control groups. The data suggests that the association of naltrexone on the development of tumours maybe dependent on tumour type. Long term exposure to naltrexone appears to have both a stimulatory and inhibitory effect on tumours in rats, dependent on tumour type.

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Hormonal Influences on Mammary Tumors of the Rat

Cited by 32 publications

References 14 publications

Hormonal Influences on Mammary Tumors of the Rat

Hormonal Influences on Mammary Tumors of the Rat

Rapid Induction of Mammary Carcinoma in the Rat and the Influence of Hormones on the Tumors

The Occurrence of Spontaneous Lymphomas but Not Adenomas or Sarcomas in Rats Treated With Sustained Release Naltrexone

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