RESUMO
To evaluate the transgenic mouse carrying a human prototype c-Ha-ras gene (rasH2 mouse) as a model for 26-week carcinogenicity tests, Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, was administered to 15 rasH2 mice/sex/group at concentrations of 1,500, 3,000 or 6,000 ppm, and to 15 wild-type (non-Tg) mice/sex/group at a concentration of 6,000 ppm in their diets for 26 weeks. Survival rates and food consumption in the groups treated with DEHP and in the control group were similar. Body weight gain in rasH2 and non-Tg mice at 6,000 ppm in the terminal week decreased about 10% as compared to the control group. Common findings related to treatment with DEHP in rasH2 and non-Tg mice included hypertrophy with coarse granules and deposit of pigment in the liver, hydronephrosis and tubular regeneration in the kidney, focal atrophy in the testis, and increased eosinophilic body in the nasal cavity. Hepatocellular adenoma was induced by treatment with DEHP, and was confined to male rasH2; mice the incidence being 7%(1/15), 13%(2/15), and 27%(4/15) in the 1,500-, 3,000-, and 6,000-ppm group, respectively. Point mutation was not detected in codon 12 and 61 of human c-Ha-ras transgene upon DNA analyses on frozen samples taken from these hepatocellular adenomas. From the results obtained in this 26-week carcinogenicity study, it is concluded that DEHP is a hepato-carcinogen for transgenic mouse carrying a human prototype c-Ha-ras gene.
Assuntos
Adenoma de Células Hepáticas/genética , Dietilexilftalato/toxicidade , Genes ras , Neoplasias Hepáticas Experimentais/genética , Proliferadores de Peroxissomos/toxicidade , Adenoma de Células Hepáticas/induzido quimicamente , Adenoma de Células Hepáticas/patologia , Administração Oral , Animais , Testes de Carcinogenicidade/métodos , Dietilexilftalato/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Transgênicos , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/patologia , Proliferadores de Peroxissomos/administração & dosagem , Polimorfismo Conformacional de Fita Simples , Fatores Sexuais , Taxa de Sobrevida , Testículo/efeitos dos fármacos , Testículo/patologia , Fatores de TempoRESUMO
A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Sprague-Dawley strain in Japan, and named the rising "Nihon" rat. In this strain, RCs develop from early preneoplastic lesions, which begin to appear at 4 weeks of age, forming adenomas by the age of 16 weeks. The RCs are predominantly of clear cell type. Southern blot, northern blot and SSCP analyses revealed no change in the Tsc1, Tsc2, VHL, and c-Met genes. Thus, the Nihon rat should be a valuable experimental model for understanding renal carcinogenesis, especially clear cell type, which is common among human RCs.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Ligases , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Animais , Northern Blotting , Southern Blotting , Carcinoma de Células Renais/patologia , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Genes Dominantes/genética , Genes Supressores de Tumor , Neoplasias Renais/patologia , Masculino , Mutação , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita Simples , Proteínas/genética , Proteínas Proto-Oncogênicas c-met/genética , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/genética , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Proteína Supressora de Tumor Von Hippel-LindauRESUMO
An ovarian choriocarcinoma was found in a 13-year-old cynomolgus monkey (Macaca fascicularis). The tumor was accompanied by a mature teratoma in the contralateral ovary. Histologically, the choriocarcinoma was characterized by nests of cells where cytotrophoblasts occupied the periphery with syncytiotrophoblasts at the center. Immunohistochemical staining for anti-human chorionic gonadotropin was positive in the syncytiotrophoblasts. The teratoma consisted of well-differentiated epidermal cells, sebaceous glands, hair follicles, cartilage, bone, and teeth. Choriocarcinoma metastases were in multiple organs. The concomitant development of choriocarcinoma and teratoma in the ovary is a consistent finding with the human counterparts of these lesions.
Assuntos
Coriocarcinoma/veterinária , Macaca fascicularis , Doenças dos Macacos/patologia , Neoplasias Primárias Múltiplas/veterinária , Neoplasias Ovarianas/veterinária , Teratoma/veterinária , Anemia/veterinária , Animais , Coriocarcinoma/patologia , Evolução Fatal , Feminino , Imuno-Histoquímica , Neoplasias Primárias Múltiplas/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Hemorragia Uterina/veterináriaRESUMO
OBJECTIVE: To characterize clinical findings associated with mutations in codon 244 (Asn244His) and codon 184 (Tyr184Ser) of the peripherin/RDS gene. DESIGN: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, and DNA analysis. SETTING: University medical center. PATIENTS: Four affected members of two Japanese families with autosomal dominant cone-rod dystrophy associated with transversion mutations in codon 244 (Asn244His) and codon (Tyr184Ser) of the peripherin/RDS gene. RESULTS: Characteristic features included the initial symptoms of decreased visual acuity, macular degeneration, central or paracentral scotoma, cone-mediated electroretinographic responses that were more impaired than rod-mediated responses, and pigmentary degeneration in the midperipheral retina in the late stage. These phenotypic features corresponded to cone-rod dystrophy type 2a by the classification of Szlyk and associates. CONCLUSIONS: The Asn244His and Tyr184Ser mutations in the peripherin/RDS gene cause con-rod dystrophy type 2a. These findings imply that a mutation in codon 244 or codon 184 of the peripherin/RDS gene affects the functions and/or structural stability of cones and rods.
Assuntos
Códon/genética , Proteínas do Olho/genética , Proteínas de Filamentos Intermediários/genética , Proteínas do Tecido Nervoso , Células Fotorreceptoras/patologia , Mutação Puntual , Degeneração Retiniana/genética , Adulto , Idoso , Sequência de Aminoácidos , Asparagina , Sequência de Bases , DNA/análise , Eletrorretinografia , Feminino , Angiofluoresceinografia , Histidina , Humanos , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Periferinas , Polimorfismo Conformacional de Fita Simples , Degeneração Retiniana/patologia , Serina , Tirosina , Campos VisuaisRESUMO
OBJECTIVE: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. DESIGN: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. SETTING: University medical center. PATIENTS: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. RESULTS: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. CONCLUSION: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown.
Assuntos
Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana , Mutação , Proteínas do Tecido Nervoso , Neuropeptídeos/genética , Retinose Pigmentar/genética , Adulto , Asparagina , Sequência de Bases , Criança , Códon , Feminino , Genes Dominantes , Humanos , Lisina , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , PeriferinasAssuntos
Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso , Mutação Puntual , Retinose Pigmentar/genética , Sequência de Aminoácidos , Sequência de Bases , Códon/genética , Eletrorretinografia , Feminino , Genes , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Degeneração Neural , Periferinas , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Retinose Pigmentar/classificaçãoAssuntos
Proteínas de Filamentos Intermediários/genética , Macula Lutea , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso , Mutação Puntual , Doenças Retinianas/genética , Retinose Pigmentar/genética , Sequência de Aminoácidos , Sequência de Bases , DNA/genética , Genes Dominantes , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Periferinas , Polimorfismo Genético , Doenças Retinianas/complicações , Retinose Pigmentar/complicaçõesRESUMO
The contribution of oceanic gabbros, representative rocks for layer 3 of the oceanic crust, to sea-floor spreading magnetic anomalies has been controversial because of the large variation in magnetic properties. Ocean Drilling Program (ODP) Leg 118 contains a continuous 500.7-meter section of oceanic gabbro that allows the relations between magnetization and petrologic characteristics, such as the degree of metamorphism and the magmatic evolution, to be clarified. The data suggest that oceanic gabbros, together with the effects of metamorphism and of magmatic evolution, account for a significant part of the marine magnetic anomalies.
