ergoline and Precancerous-Conditions

The general characteristics of the preneoplastic lesions of the human mammary gland, as they are known through histologic description, are outlined, and data obtained from the experimental analysis of mammary gland preneoplasia in five areas of endeavor are discussed. Results obtained with transplantation procedures and aimed at defining the growth potential of hyperplastic outgrowths are reported. Information derived from the study of events able to induce benign hyperplastic outgrowths or their malignant transformation in the murine mammary gland is summarized. Attempts to predict neoplastic transformation in morphologically hyperplastic epithelium of human and rodent glands are discussed. The present status of efforts toward the prophylaxis of preneoplastic lesions of the mammary gland is described. Considerations of the relationship between preneoplasia and tumor dormancy conclude the presentation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Breast; Breast Neoplasms; Bromocriptine; Cell Transformation, Neoplastic; Cells, Cultured; Ergolines; Female; Humans; Hyperplasia; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Neoplasm Transplantation; Precancerous Conditions; Transplantation, Heterologous; Urethane

The tumor potentials of five preneoplastic mammary nodule lines were examined in BALB/cCrgl mice treated with either nafoxidine, an estrogen antagonist; 2-bromo-alpha-ergocryptine, a prolactin suppressant; or testosterone. The inhibitory effect of any of the three agents was dependent on the individual nodule line and was not correlated with the effects of ovariectomy. Nafoxidine inhibited tumor formation only in nodule line D2; testosterone inhibited tumor formation in lines C3 and C4; and 2-bromo-alpha-ergocryptine failed to inhibit tumor formation in any of the nodule lines. These results provided information on the range of responses of mouse preneoplastic mammary tissues to a variety of antihormone treatments and suggested that responses to ovariectomy need not be correlated with responses to specific antihormone treatments.

Topics: Animals; Bromocriptine; Ergolines; Female; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Nafoxidine; Neoplasm Transplantation; Ovary; Precancerous Conditions; Pyrrolidines; Receptors, Androgen; Receptors, Estrogen; Testosterone; Transplantation, Isogeneic

We compared the effects of chronic treatment with 2-Br-alpha-ergocryptine (CB-154) and of ovariectomy on the genesis of mammary hyperplastic nodules (HN) and mammary tumors in the C3H/He mouse. CB-154 is an established potent suppressor of pituitary prolactin. Eighty-five 21- to 25-day-old female mice were divided into three groups. Group I received daily sc injections of 0.1 mg CB-154. Group II was ovariectomized and group III served as controls. Mice were examined weekly for mammary tumors. Fifteen months from onset of treatment all surviving mice were killed. The mean number of HN per inguinal mammary gland, total number of mammary tumors, and number (percent) of mice with mammary tumors in each group were, respectively: controls--4.6 +/- 1.1, 41, 24/29 (83%); ovariectomized--1.2 +/- 0.6, 20, 14/28 (50%); and CB-154-treated--0.2 +/- 0.1, 16, 13/28 (46%). A significant (P less than 0.001) and equally comparable inhibition of mammary tumor incidence was observed in the ovariectomized and CB-154-treated mice. Thus early ovariectomy and CB-154 treatment (specific inhibition of prolactin secretion) appeared equally effective in the prophylaxis of mammary tumorigenesis in the C3H/He female mouse.

Topics: Adrenal Glands; Animals; Bromocriptine; Castration; Ergolines; Female; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Precancerous Conditions; Prolactin

Daily treatment (for 12 to 14 months) of 2-month-old nulliparous or 8-month-old multiparous C3H/HeJ mice with 0.1 mg of 2-bromo-alpha-ergocryptine (CB-154) or 6-methyl-8-beta-ergoline-acetonitrile, efficacious inhibitors of prolactin secretion, markedly reduced the incidence of spontaneous mammary hyperplastic nodules and mammary tumors. CB-154 appeared to be more effective than 6-methyl-8-beta-ergoline-acetonitrile in suppressing the incidence of mammary tumors; the ergot virtually prevented the appearance of mammary tumors in nulliparous mice. Daily treatment of 5-month-old estrogen-treated, ovariectomized-hysterectomized C3H/HeJ mice for 12 months with CB-154 also significantly reduced the incidence of hyperplastic nodules and mammary tumors when compared with ovariectomized-hysterectomized mice treated with steroid alone. Daily treatment of multiparous C3H/HeJ mammary tumor-bearing mice with CB-154 or 6-methyl-8-beta-ergoline-acetonitrile generally failed, however, to promote regression of the mammary tumors. Thus significant prophylaxis of early preneoplastic lesions by drug-induced hormone (prolactin) suppression, resulting in a marked reduction in mammary tumor incidence, has been demonstrated in this study.

Topics: Animals; Bromocriptine; Ergolines; Female; Hyperplasia; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Metergoline; Mice; Mice, Inbred C3H; Parity; Precancerous Conditions; Prolactin

Topics: Acetonitriles; Adrenal Glands; Animals; Body Weight; Ergolines; Estrus; Female; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Organ Size; Ovary; Parity; Pituitary Gland; Precancerous Conditions; Pregnancy; Uterus