RESUMEN
This study compares the relative biological potencies of a known antiestrogen tamoxifen to two triarylethylene compounds which have been shown previously to be potent inhibitors of rodent mammary tumorigenesis. Based on a) uterotrophic and anti-uterotrophic tests, b) indexes of cellularity, and c) protein content, these studies indicate that the trans, as well as the cis, isomers of bromotriphenylethylene are partial estrogen antagonists with no estrogenic effects in rat uteri and partial agonists in mouse uteri, whereas tamoxifen shows partial antiestrogenic/estrogenic effects in rats and is fully estrogenic in mice.
Asunto(s)
Antagonistas de Estrógenos , Estilbenos/farmacología , Tamoxifeno/farmacología , Animales , ADN/análisis , Femenino , Ratones , Tamaño de los Órganos/efectos de los fármacos , Proteínas/análisis , Ratas , Estereoisomerismo , Útero/análisis , Útero/crecimiento & desarrolloRESUMEN
The plasma levels of ovarian steroids and the steroid binding capacity in the cytosol of mammary glands have been determined in the low-mammary-tumor C3H/f (XVII) mice. Implantation of a pituitary under the kidney leads to an increase of all these parameters as well as a high mammary tumor incidence. Simultaneous administration of the trans isomer of broparestrol (TBP) leads to a decrease of all the parameters.
Asunto(s)
Neoplasias Mamarias Experimentales/metabolismo , Ovario/metabolismo , Prolactina/fisiología , Animales , Estradiol/metabolismo , Femenino , Ratones , Hipófisis/efectos de los fármacos , Hipófisis/trasplante , Progesterona/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Progesterona/metabolismo , Estilbenos/farmacología , Trasplante HomólogoRESUMEN
The trans isomer of a bromotriphenylethylene (TBP) inhibits spontaneous mammary carcinogenesis in (C3H x RIII)F1 females, which received a diet containing 20 ppm of the chemical: intact, spayed, and spayed and pituitary implanted animals. Mammary carcinogenesis is inhibited even if the administration of the compound starts late in life. TBP has no activity on mammary carcinogenesis of castrated males implanted with an ovary.
Asunto(s)
Antagonistas de Estrógenos/farmacología , Neoplasias Mamarias Experimentales/prevención & control , Estilbenos/farmacología , Animales , Castración , Antagonistas de Estrógenos/administración & dosificación , Femenino , Isomerismo , Masculino , Ratones , Hipófisis/fisiologíaRESUMEN
C3Hf (XVII) mice never develop spontaneous mammary tumors. However, the transplantation of an isologous pituitary gland under their kidney capsule is followed by a 10-fold increase in serum and pituitary prolactin content (180 ng/ml and 20 micrograms/mg of tissue, respectively), concomitant with an increase of prolactin receptors in mammary glands. Under these conditions, mammary tumors appear in 90% of the mice. If a racemic brominated triphenylethylene, i.e., broparestrol, is administered, serum and pituitary prolactin decrease rapidly (10 ng/ml and 4 micrograms/mg of tissue, respectively), and prolactin receptors in the mammary gland are markedly reduced. This compound also inhibits the development of normal mammary glands, prevents mammary carcinogenesis, and unexpectedly causes a significant atrophy of the ovaries. Our study confirms that prolactin is a key hormone involved in murine mammary carcinogenesis and that it can act directly on the mammary gland by stimulaing the level of its own receptor.
Asunto(s)
Neoplasias Mamarias Experimentales/inducido químicamente , Prolactina , Estilbenos/farmacología , Animales , Femenino , Ratones , Ratones Endogámicos C3H , Hipófisis/trasplante , Prolactina/antagonistas & inhibidores , Prolactina/sangre , Receptores de Superficie Celular/metabolismo , EstereoisomerismoRESUMEN
Daily administration of a brominated triphenylethylene (TBP), to rats which received 20 mg of DMBA p. o. inhibits mammary carcinogenesis. The effect appears even with very small doses (i ppm in the diet) and seems to be dose related. With one exception (an adenofibroma) the tumours in control and treated animals were malignant. Administration of TBP prevents the appearance of corporea lutea in the ovaries but not the usual necrosis of the adrenal cortex.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/antagonistas & inhibidores , Benzo(a)Antracenos/antagonistas & inhibidores , Congéneres del Estradiol/farmacología , Neoplasias Mamarias Experimentales/prevención & control , Estilbenos/farmacología , Adenocarcinoma/prevención & control , Adenofibroma/prevención & control , Corteza Suprarrenal/patología , Animales , Cuerpo Lúteo/efectos de los fármacos , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Necrosis/inducido químicamente , Tamaño de los Órganos/efectos de los fármacos , Ovario/patología , RatasRESUMEN
The effect of administration of thiourea (5 g/kg in diet) alone or simultaneously with thyroxine (1 mg/l in drinking water) on the frequency of hyperplastic benign osteoma of the skull was studied in AkR mice. Animals treated with both thiourea and thyroxine were in hyperthyroidism: the thyroxine dose received was higher that that required to prevent thiourea-induced thyroid gland hypertrophy. A significant increase of the intracranial bone tumour (IBT) frequency was observed both in mice treated with thiourea alone and those which received thiourea and thyroxine simultaneously. Increase of IBT frequency was not due to the antithyroid effect of thiourea but seems due to a direct toxic action of thiourea on the pituitary.
Asunto(s)
Osteoma/etiología , Hipófisis/efectos de los fármacos , Neoplasias Craneales/etiología , Tiourea/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos AKR , Neoplasias Experimentales/etiología , Glándula Tiroides/efectos de los fármacos , Tiroxina/administración & dosificaciónRESUMEN
Hexachlorophene (HCP) was tested for carcinogenicity in lifetime feeding studies in male Sprague--Dawley rats that were fed on a protein- and vitamin-deficient diet and in C57B1 and XVII/G mice that received the chemical incorporated into a complete diet. After 2 years, no significant carcinogenic effects were observed in these animals. In XVII/G mice injected subcutaneously at birth or receiving HCP via the mother's milk, the incidence of tumors was not statistically increased. No carcinogenic effect was observed in (C57B1 X C3H) F1 hybrid mice that received HCP transplacentally.
Asunto(s)
Carcinógenos , Hexaclorofeno/toxicidad , Administración Oral , Factores de Edad , Animales , Femenino , Hexaclorofeno/administración & dosificación , Lactancia , Masculino , Intercambio Materno-Fetal , Ratones , Ratones Endogámicos , Embarazo , Ratas , Factores de TiempoRESUMEN
Administration of a bromotriphenylethylene to C3H/f(XVII/G) female mice implanted with a pituitary under the kidney capsule produces with high doses (200 mg/kg or 20 mg/kg of diet) a strong inhibition of the development of the mammary glands. With a low dose (2 mg/kg) no inhibition was observed. In mice which received the high doses no hyperplastic alveolar nodules were observed. The activity of the compound is more pronounced after 50 days than after 25 days.
Asunto(s)
Glándulas Mamarias Animales/efectos de los fármacos , Estilbenos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Glándulas Mamarias Animales/crecimiento & desarrollo , Ratones , Ratones Endogámicos C3H , Hipófisis/fisiología , Hipófisis/trasplante , Trasplante IsogénicoRESUMEN
Castrated male (C3H X RIII) F1 mice were treated with graded doses of estradiol-17-beta and estrone in a life-span experiment. Estradiol-17-beta incorporated into paraffin pellets was implanted under the skin for continuous resorption. These pellets contained 1 microgram, 2.5 microgram, 5 microgram, 10 microgram or 100 microgram of hormone. Estron was given orally, mixed with the food at 3 daily dosages: 0.06 microgram, 0.6 microgram and 6 microgram. Although the smallest dosages of both hormones induced vaginal estrus in castrated females, they did not produce mammary tumors. The mammary tumor incidence reached progressively almost 100% in response to the increase of the hormonal dosages. The absence of effect of low doses of estrogen in mice is compared with the absence of an excess of breast cancers among women using oral contraceptives.
Asunto(s)
Estradiol , Estrona , Neoplasias Mamarias Experimentales/inducido químicamente , Animales , Carcinógenos , Castración , Relación Dosis-Respuesta a Droga , Implantes de Medicamentos , Estradiol/administración & dosificación , Estrona/administración & dosificación , Estro/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos , EmbarazoRESUMEN
Administration of bromotriphenylethylene to C3H/f female mice implanted with a pituitary under the kidney capsule produce an inhibition of mammary carcinogenesis with high doses (20 ppm or 200 ppm in the diet). With a diet containing 2 ppm no inhibition is observed.
Asunto(s)
Congéneres del Estradiol/uso terapéutico , Neoplasias Mamarias Experimentales/prevención & control , Estilbenos/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Ratones Endogámicos , HipófisisRESUMEN
In (C3H X RIII) F1 females a disturbed hormonal balance plays the major role for the etiology of mammary carcinomas. Castration early in life delays the appearance of the tumors. In normal females the adrenal secretions do not intervene in carcinogenesis. In forced bred females or in animals with pseudopregnancies, but not in mothers which nursed their offspring the latencies are shortened. After a graft with one male pituitary to a castrated female the latency is the same as in intact animals. Pituitary grafting to castrated males does not change the frequency or the latencies of spontaneous mammary cancers. One mammary cancer was observed in an intact male implanted with a pituitary. It is stated that in our animal model progesterone is not an essential factor for mammary carcinogenesis.
Asunto(s)
Neoplasias Mamarias Experimentales/etiología , Animales , Castración , Femenino , Hibridación Genética , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos , Hipófisis/trasplante , Embarazo , Seudoembarazo , Trasplante HomólogoRESUMEN
Adult mice of strains C3Hf and XVII/G received 2, 4, 5-T by continuous oral administration (80 ppm in the diet). The 2, 4, 5-T preparation contained less than 0-05 ppm of dioxins. In 2, 4, 5-T -treated C3Hf mice a significant increase in the incidence of neoplastic lesions was found. No significant difference was found in the XVII/G strain between the treated and control mice. Rare forms of tumours, which were not observed in the controls, were present in the 2, 4, 5-t -treated C3Hf mice.
Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/toxicidad , Neoplasias Experimentales/inducido químicamente , Animales , Carcinoma Hepatocelular/inducido químicamente , Dioxinas/toxicidad , Femenino , Leucemia Experimental/inducido químicamente , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos , Factores SexualesRESUMEN
Gamma-butyrolactone has been tested for its carcinogenic activity in pure strain XVII/G and C3H Mice. No tumours were observed in mice which received the compound in injections at birth, after skin painting, gavage, or mixed with their food.
Asunto(s)
4-Butirolactona , Furanos , Animales , Femenino , Neoplasias Pulmonares/inducido químicamente , Masculino , Neoplasias Mamarias Experimentales/inducido químicamente , Ratones , Neoplasias Experimentales/inducido químicamenteRESUMEN
Administration of sulpiride mixed with the food during the whole life, did not modify spontaneous mammary carcinogenesis of intact, castrated or adrenalectomized and castrated (C3H X R III) F1 male and female mice.