RESUMEN
Repeated dose (14 days), subchronic (13 wk) and chronic (2 yr) studies were carried out in succession to evaluate the toxic and carcinogenic effects of diglycidyl resorcinol ether (DGRE), a liquid spray epoxy resin, in F344/N rats and B6C3F1 mice. DGRE in corn oil was administered by gavage for 14 consecutive days in the repeated dose study and 5 days/wk in the subchronic and chronic studies. The mortality rate was increased in rats and mice in the repeated dose and subchronic studies. Hyperkeratosis, basal cell hyperplasia and squamous cell papillomas of the forestomach were observed in a few treated rats and mice in the subchronic study. Based on the results of the subchronic study, F344/N rats and B6CF1 mice (50 males and 50 females/species/dose) were administered DGRE (rats--0, 12, 25 and 50 mg/kg body weight, mice--0, 50 and 100 mg/kg body weight) in corn oil by gavage 5 days/wk for 103 wk. The incidence of neoplastic and non-neoplastic changes of the forestomach was increased in rats and mice in the chronic study. Under the conditions of the study, DGRE is considered to be carcinogenic to F344/N rats and B6C3F1 mice.
Asunto(s)
Carcinógenos/toxicidad , Papiloma/inducido químicamente , Resorcinoles/toxicidad , Neoplasias Gástricas/inducido químicamente , Animales , Peso Corporal/efectos de los fármacos , Femenino , Hiperplasia , Hígado/efectos de los fármacos , Masculino , Ratones , Ratas , Ratas Endogámicas F344 , Estómago/efectos de los fármacos , Estómago/patologíaRESUMEN
F344 rats of both sexes were fed one of three concentrations (0.02, 0.04, 0.05%) of 4,4'-oxydianiline (CAS: 101-80-4), an intermediate in the manufacture of polyimide resins, mixed in the diet for 2 years. The incidence of hepatocellular neoplasms was increased in all the 3 groups of male rats and in female rats of the middle- and high-dose groups. The incidence of hyperplastic and neoplastic changes in the follicular cells of the thyroid gland was increased in male and female rats of the middle- and high-dose groups. The population of thyrotrophs (thyrotropin-producing cells) was increased in the pituitary glands of rats with neoplasms of the thyroid gland. These cells were distinct from prolactin cells. The increase in the number of thyrotrophs suggested insufficient hormone production by the induced thyroid tumors.
Asunto(s)
Carcinógenos , Éteres Fenílicos/farmacología , Hipófisis/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Animales , Femenino , Hiperplasia/inducido químicamente , Técnicas para Inmunoenzimas , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Éteres Fenílicos/administración & dosificación , Hipófisis/metabolismo , Hipófisis/patología , Ratas , Ratas Endogámicas F344 , Glándula Tiroides/patología , Neoplasias de la Tiroides/inducido químicamente , Tirotropina/metabolismoRESUMEN
Diets containing 25,000 (2.5%) or 50,000 ppm (5.0%) agar, guar gum, gum arabic, locust-bean gum or tara gum were fed to groups of 50 male and 50 female F344 rats and B6C3F1 mice for 103 wk. Separate groups of 50 rats and 50 mice of each sex served as controls for each study. There were no significant differences in survival between any of the dosed groups of rats or mice and their respective control groups. Depressions in body-weight gain greater than 10% for dosed groups relative to their respective control groups were observed for male (low dose only) and female mice fed diets containing agar, female mice fed diets containing guar gum (high dose only), male mice fed diets containing locust-bean gum (high dose only) and male and female mice fed diets containing tara gum (high dose only). Depressions in body-weight gain greater than 5% were observed for female rats fed diets containing agar, guar gum or gum arabic. There were no histopathological effects associated with the administration of the test materials. Under the conditions of these bioassays, none of the five polysaccharides was carcinogenic for F344 rats or B6C3F1 mice of either sex.
Asunto(s)
Agar/toxicidad , Galactanos/toxicidad , Goma Arábiga/toxicidad , Mananos/toxicidad , Polisacáridos/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos , Neoplasias Experimentales/inducido químicamente , Gomas de Plantas , Ratas , Ratas Endogámicas F344RESUMEN
Twenty-one aromatic amines or derivatives were tested for long-term toxicity by dietary administration to male Charles River rats and male and female HaM/lCR mice. 2,4-Toluenediamine, o-phenylenediamine, o-toluidine, 2,4,6-trimethylaniline, 2,4,5-trimethylaniline, 2,5-xylidine, and 1-chloro-2-nitrobenzene led to tumors in one or more tissues in all three of these animal models. p-Toluidine, 4-chloro-o-toluidine and 1-chloro-4-nitrobenzene had varying degrees of activity, but in male and female mice only. 4-Chloro-4'-aminodiphenyl ether affected male rats and female mice, but there was no consistent dose response. 2,5-Dimethoxy-4'-aminostilbene led to many tumors in male rats but had only a questionable action in male mice. The effect of 3,3',4,4'tetra-aminobiphenyl in male rats was borderline; in the mice only males showed any response. In male mice 2,4,6-trichloroaniline had a fair degree of activity; tetrafluoro-m-phenylenediamine was somewhat less effective and m-toluidine had only questionable activity. 2,4-Xylidine increased lung tumors in female mice at the higher dose only. Four inactive compounds included m-phenyl-enediamine, 2,4-dinitrochlorobenzene, benzoguanamine, and dicyclopentadiene dioxide. 2,4,6-Trimethylaniline led to cirrhosis of the liver in rats only.
Asunto(s)
Aminas/toxicidad , Carcinógenos Ambientales , Animales , Diaminas/toxicidad , Femenino , Compuestos Heterocíclicos/farmacología , Dosificación Letal Mediana , Masculino , Ratones , Ratones Endogámicos ICR , Nitrobencenos/toxicidad , Compuestos Policíclicos/toxicidad , Ratas , Relación Estructura-ActividadRESUMEN
Peripheral blood and thoracic duct lymph from normal dogs and dogs with a leukemic malignant lymphoma were compared for total and differential leukocyte count and lymph flow rate. Except for higher numbers of circulating atypical lymphocytes, the blood leukocyte count as well as the lymph cell count and flow rate were similar in both groups. Lymph cell differential pattersn in lymphoma dogs had higher numbers of lymphoblasts and minor cell types, plasmacytes, monocytes, and reticulum cells, plus degenerating and mitotic cells. There was a five-fold increase in the lymph leukocyte count shortly after irradiation in two lymphomatous dosg. Stained preparations of this lymph showed signs of 100% cell mortality. It was concluded that the thoracic duct lymph is a practical source of normal and cancerous lymphoid cells, and that the lymph and cells collected from dogs with malignant lymphoma are excellent models for certain studies of spontaneous neoplasia.
Asunto(s)
Modelos Animales de Enfermedad , Enfermedades de los Perros , Linfa/fisiología , Linfocitos/patología , Linfoma , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/radioterapia , Perros , Femenino , Recuento de Leucocitos , Linfa/citología , Linfoma/sangre , Linfoma/radioterapia , Masculino , Conducto TorácicoRESUMEN
Invasive adenocarcinoma of the glandular stomach was induced in 3 BIO 87.20 inbred Syrian hamsters by the administration of 1 ppm N-nitrosodiethylamine or N-nitrosodimethylamine in the drinking water, and in 2 BIO 15.16 and 5 BIO 72.29 inbred Syrian hamsters by gavage of 3-methylcholanthrene. In contrast, many other similarly treated inbred Syrian hamster lines did not develop carcinoma of the glandular stomach. The glandular stomachs of rats and mice are resistant to polycyclic hydrocarcon carcinogenesis; however, the glandular stomachs of certain inbred Syrian hamsters develop adenocarcinoma after polycyclic hydrocarbon gavage. This work demonstrated the importance of genetic factors.
Asunto(s)
Adenocarcinoma/inducido químicamente , Dietilnitrosamina , Dimetilnitrosamina , Metilcolantreno , Nitrosaminas , Especificidad de la Especie , Neoplasias Gástricas/inducido químicamente , Adenocarcinoma/patología , Animales , Cricetinae , Femenino , Masculino , Mesocricetus , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/patología , Neoplasias Gástricas/patologíaAsunto(s)
Carcinógenos/farmacología , Nicotiana , Plantas Tóxicas , Tabaco sin Humo , Animales , Peso Corporal/efectos de los fármacos , Cotinina/sangre , Cricetinae , Depresión Química , Dieta , Sinergismo Farmacológico , Conducta Alimentaria/efectos de los fármacos , Masculino , Metilcolantreno/farmacología , Neoplasias Experimentales/inducido químicamenteRESUMEN
Three hundred CD-1 HaM/ICR mice were observed for 2 years, and useful necropsies were done on 99 males and 102 females. Mortality was 50% at 16 months in the males and 18 months in the females. Among mice that came to autopsy, total tumor incidence was 54% for males and 75% for females, with most neoplasms occurring after 18 months. Adenomas or adenocarcinomas of the lung were the most frequent, followed by lymphoreticular tumors, vascular tumors, hepatomas, subcutaneous fibrosarcomas, and adenocarcinomas of the mammary glands. Some degree of amyloidosis was seen in half the mice of both sexes, beginning at 8 months in males and 12 months in females. Variability in tumor incidence among small groups if mice emphasized the need for adequate samples.
Asunto(s)
Envejecimiento , Ratones Endogámicos ICR/crecimiento & desarrollo , Neoplasias/veterinaria , Enfermedades de los Roedores/epidemiología , Adenocarcinoma/epidemiología , Adenoma/epidemiología , Glándulas Suprarrenales/patología , Amiloidosis/epidemiología , Animales , Peso Corporal , Carcinoma Hepatocelular/epidemiología , Enfermedades Cardiovasculares/epidemiología , Femenino , Genitales/patología , Esperanza de Vida , Neoplasias Hepáticas/epidemiología , Neoplasias Pulmonares/epidemiología , Linfoma/epidemiología , Masculino , Ratones , Ratones Endogámicos ICR/anatomía & histología , Neoplasias/epidemiología , Factores SexualesRESUMEN
Production of Sheehan's syndrome was attempted. As it was not possible to obtain pregnant baboons initially, pseudopregnancy was induced with norlestrin, 2.k mg., for 3 and 4 months, respectively. Sheehan's syndrome was not produced with massive hypovolemic shock but failure to obtain true pregnancy has given serendipitous information on the long-term action of norlestrin on the pituitary and its target organs. Unusual abundance of prolactin acidophils and decrease of growth hormone acidophils was found. Further studies will be necessary to show the possible significance of these findings. As fibrin degradation products did not appear in the serum, we can make no inference about the necessity of intravascular coagulation for the production of Sheehan's phenomenon. Finally one animal became pregnant. Sheehan's phenomenon was not produced in her despite induction of intrapartum hypovolemic shock. Histologic findings in her pituitary resemble those of the pseudopregnant animals.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Glándulas Endocrinas/efectos de los fármacos , Etinilestradiol/farmacología , Hipopituitarismo/inducido químicamente , Seudoembarazo , Animales , Pruebas de Coagulación Sanguínea , Glucemia/análisis , Femenino , Haplorrinos , Hemodinámica/efectos de los fármacos , Microscopía Electrónica , Papio , Hipófisis/efectos de los fármacos , Hipófisis/ultraestructura , Embarazo , Pruebas de Función de la Tiroides , Útero/citologíaRESUMEN
Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan.