Asunto(s)
Adyuvantes Inmunológicos/farmacología , Vacuna BCG/farmacología , Clenbuterol/farmacología , Hematopoyesis/efectos de los fármacos , Leucemia Experimental/tratamiento farmacológico , Virus Rauscher , Suramina/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Vacuna BCG/uso terapéutico , Médula Ósea/efectos de los fármacos , Clenbuterol/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Leucemia Experimental/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Suramina/uso terapéutico , Factores de TiempoRESUMEN
A system for evaluating the activity of antiviral agents against Rauscher murine leukemia virus (R-MuLV) has been developed using an enzyme linked immunosorbent assay technique. The activity of various antiviral compounds demonstrated in this assay system has been compared to their activity in the UV-XC plaque reduction assay, which has been used historically for evaluating anti-R-MuLV compounds. The assay is based upon detection of R-MuLV encoded p30 protein production in virus infected murine cells. The assay reagents are readily available and the assay system is amenable to automated data collection systems. Cytotoxicity evaluations are conducted in parallel to the Rauscher MuLV ELISA assay in order to assess drug-induced reductions in cell viability. Cytotoxicity evaluations are important to interpretation of the ELISA results since reductions in cell viability reduce viral protein production which would indicate an antiviral drug effect. This system is less sensitive than the classical UV-XC plaque reduction assay; however, it does offer an alternative to the time-consuming and labor-intensive plaque assay.
Asunto(s)
Antivirales/uso terapéutico , Ensayo de Inmunoadsorción Enzimática/métodos , Leucemia Experimental/tratamiento farmacológico , Virus Rauscher , Animales , Antivirales/metabolismo , Ratones , Pruebas de Sensibilidad Microbiana/métodos , Ensayo de Placa ViralAsunto(s)
Antivirales/toxicidad , Actividad Motora/efectos de los fármacos , Neurotoxinas/toxicidad , Reflejo de Sobresalto/efectos de los fármacos , Zalcitabina/toxicidad , Estimulación Acústica , Animales , Antivirales/uso terapéutico , Peso Corporal/efectos de los fármacos , Perros , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Haplorrinos , Leucemia Experimental/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos BALB C , Conejos , Ratas , Ratas Endogámicas , Virus RauscherRESUMEN
An antileukemic activity of partially purified polysaccharide of an edible seaweed. Viva-Natural, against Rauscher murine retrovirus-induced erythroleukemia has been demonstrated. This antileukemic effect is compared with standard anti-human immunodeficiency virus (HIV) agents, azidothymidine (AZT), dextran sulfate and pentosan polysulfate. Pretreatment with Viva-Natural, as an immunomodulator, on day 3 prior to the virus inoculation demonstrated definite prophylactic activity, while pretreatment with the other three anti-HIV agents showed no prophylactic activity. The replication of Rauscher virus in BALB/3T3 cell cultures accompanied by direct cytopathic effect (syncytia formation) was suppressed in the presence of Viva-Natural or the other anti-HIV agents in the culture medium. In spite of the antiviral potentials of the four agents in vitro, only Viva-Natural and AZT demonstrated therapeutic efficacy against Rauscher leukemia in mice.
Asunto(s)
Antineoplásicos/uso terapéutico , Sulfato de Dextran/uso terapéutico , Leucemia Experimental/prevención & control , Poliéster Pentosan Sulfúrico/uso terapéutico , Extractos Vegetales/uso terapéutico , Virus Rauscher/efectos de los fármacos , Zidovudina/uso terapéutico , Animales , Línea Celular , Femenino , VIH/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Virus Rauscher/crecimiento & desarrollo , Algas Marinas , Esplenomegalia/prevención & controlRESUMEN
A traditional Kampo drug, Sho-saiko-to, composed of several herb extracts, differentially inhibited the activities of reverse transcriptase and human cellular DNA polymerase alpha and beta. Reverse transcriptases from murine leukemia virus and human immunodeficiency virus were inhibited by over 80% and 50%, respectively, in the presence of 100 micrograms/ml Sho-saiko-to, whereas DNA polymerase alpha was much less sensitive to inhibition by this drug than were the reverse transcriptases. DNA polymerase gamma was not inhibited by this drug at concentrations of up to 500 micrograms/ml. Only DNA polymerase beta was moderately inhibited by Sho-saiko-to. Thus, it has been shown that the inhibition by Sho-saiko-to is relatively specific for reverse transcriptase and that the drug contains as yet unidentified inhibitory substance(s) for reverse transcriptase.
Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China , Inhibidores de la Síntesis del Ácido Nucleico , Inhibidores de la Transcriptasa Inversa , Animales , ADN Polimerasa Dirigida por ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Transcriptasa Inversa del VIH , VIH-1/enzimología , Humanos , Ratones , Virus de la Leucemia Murina de Moloney/enzimología , Virus Rauscher/enzimologíaRESUMEN
Rauscher murine leukemia virus (RLV) infection of adult mice results in splenomegaly that is proportional to the virus titer. We have used this model to study the therapy of chronic viremia as well as chemoprophylaxis after viral exposure, both with single agents and with combination therapy. We showed that prompt initiation of effective antiviral therapy after viral exposure can prevent de novo infection. We have also developed a murine neurotropic retrovirus model which allows analysis of candidate antiviral agents for activity across the blood-brain barrier. This model can also be used to study therapeutic approaches to retroviral infections acquired at midgestation or during the neonatal period.
Asunto(s)
Modelos Animales de Enfermedad , Leucemia Experimental/tratamiento farmacológico , Ratones Endogámicos BALB C , Infecciones por Retroviridae/tratamiento farmacológico , Zidovudina/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Animales , Terapia Combinada , Evaluación Preclínica de Medicamentos , Interferón Tipo I/uso terapéutico , Virus de la Leucemia Murina/efectos de los fármacos , Leucemia Experimental/prevención & control , Leucemia Experimental/terapia , Ratones , Virus Rauscher/efectos de los fármacos , Proteínas Recombinantes , Retroviridae/efectos de los fármacos , Infecciones por Retroviridae/prevención & control , Infecciones por Retroviridae/terapia , Viremia/tratamiento farmacológico , Viremia/prevención & control , Viremia/terapiaRESUMEN
An aqueous extract from the marine red alga, Schizymenia pacifica has been tested in a cell free system for its effect on reverse transcriptase from avian retrovirus (avian myeloblastosis virus), and mammalian retrovirus (Rauscher murine leukemia virus). The extract inhibited reverse transcriptase from both these retroviruses but showed almost no effect, if any, on the activity of cellular DNA polymerase alpha and RNA polymerase II in vitro. Consequently it is unlikely to have an adverse effect on the growth of cultured cell. The inhibitory activity of the extract was stable over a relatively wide pH range (pH 1-11) and was not lost after pronase digestion. Inhibitory activity of the extract was lost after boiling at 100 degrees C in 0.67 N HCl, and after treatment with 100 mM NaIO4. The active principle in the extract has an apparent molecular weight in excess of 100,000 daltons. This new reverse transcriptase inhibitor is probably a polysaccharide.
Asunto(s)
Antivirales , Extractos Vegetales/farmacología , Retroviridae/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa , Rhodophyta , Virus de la Mieloblastosis Aviar , ADN/biosíntesis , Peso Molecular , ARN/biosíntesis , Virus Rauscher/efectos de los fármacosRESUMEN
Starting with a brief outline of the general toxic effects of selenium compounds, their biological importance for the organism as a trace element and with an analysis of the different hypotheses on the action mechanism of selenium and selenium compounds, a survey is provided in which way selenium compounds may influence malignant transformation and related processes in vivo and in vitro. Furthermore, observations are viewed on the effects of selenium compounds on spontaneously developing, chemically or virally induced tumors. Based on the data available so far it cannot, at present, be assessed whether selenium and its compounds can be used in the future for chemoprevention of cancer.
Asunto(s)
Selenio/fisiología , Animales , Antineoplásicos/fisiología , Cricetinae , Leucemia Experimental/prevención & control , Ratones , Ratas , Virus Rauscher , OligoelementosAsunto(s)
Retroviridae/efectos de los fármacos , Selenio/farmacología , Replicación Viral/efectos de los fármacos , Animales , Femenino , Virus de la Leucemia Bovina/enzimología , Leucemia Experimental/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos BALB C , Virus Rauscher/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa , Ácido SeleniosoRESUMEN
A modified in vitro transformation assay demonstrated potential for use in the identification and study of tumor promoters. Rauscher murine leukemia virus-infected F344 rat embryo cells were transformable by various chemical carcinogens when they were administered at appropriate doses. Cells treated with subeffective doses of 3-methylcholanthrene did not transform. However, when these cells were regularly treated with 12-O-tetradecanoylphorbol 13-acetate, sodium phenobarbital, limonene, oleic acid, lauric acid, or saccharin, transformation was observed. Thus several dhemically diverse in vivo tumor promoters behaved as promoters in this in vitro system. This assay appeared to be useful for in vitro efforts to identify promoters and may be of value in studies on the mechanisms of action of these cocarcinogens.
Asunto(s)
Transformación Celular Neoplásica/inducido químicamente , Cocarcinogénesis , Evaluación Preclínica de Medicamentos/métodos , Metilcolantreno , Animales , Carcinógenos , Transformación Celular Viral , Células Cultivadas , Embrión de Mamíferos , Virus de la Leucemia Murina , Ratas , Virus RauscherRESUMEN
The development of standardized assay procedures has permitted the exploitation of cell culture systems as bioassay tools for the detection of chemical carcinogens. These systems fall generally into 3 classes: diploid cell strains, Syrian hamster embryo cells; cell lines, mouse BALB/c-3T3 and mouse C3H-10T1/2; and cells+virus, Fischer rat cells infected with Rauscher leukemia virus and Syrian hamster embryo cells infected with adenovirus. The results accumulated to date show a good correlation between transformation response in cell culture and carcinogenicity of chemicals in whole animal studies. The major advantages of these systems are their relative brevity (10 days-6 weeks) and resultant low costs, their agreement with whole animal bioassays, and their direct biological relevance to the carcinogenic process. The present major disadvantages are the uncertain nature of the metabolic capabilities of the target cells and the lack of a metabolic activation system that is reliable and adaptable for routine bioassays. The development of epithelial cell systems such as breast, liver, lung, and skin may solve the problem of carcinogen metabolism as well as provide target cells that are representative of major organ sites for cancer in man. The rational use of cell culture bioassays for neoplastic transformation is a valuable component of the toxicological armamentarium to assess risk to humans from exposure to chemicals.
Asunto(s)
Carcinógenos/toxicidad , Transformación Celular Neoplásica , Adenoviridae , Animales , Transformación Celular Viral , Células Clonales , Cricetinae , Evaluación Preclínica de Medicamentos/métodos , Embrión de Mamíferos , Fibroblastos , Humanos , Técnicas In Vitro , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratas , Virus RauscherAsunto(s)
Carcinógenos , Transformación Celular Neoplásica/inducido químicamente , Evaluación Preclínica de Medicamentos/métodos , Leucemia Experimental/patología , Agar , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo , Femenino , Embarazo , Ratas , Virus RauscherRESUMEN
Pretazettine hydrochloride (PTZ) has been found to inhibit protein synthesis, without being inhibitory to DNA and RNA, in Rauscher leukemic blood cells in mice for at least 6 h after its administration. With comparison to Virazole and cycloheximide, the specific anti-Rauscher virus activity of PTZ has been demonstrated only in acutely-infected NIH/3T3 cells but not in chronically-infected cells. It is not certain that the inhibitory action of PTZ on reverse transcriptase is contributory to its therapeutic activity in leukemic mice.
Asunto(s)
Alcaloides/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia Experimental/tratamiento farmacológico , Animales , Línea Celular , Pruebas Inmunológicas de Citotoxicidad , ADN de Neoplasias/biosíntesis , ADN Polimerasa Dirigida por ADN/metabolismo , Evaluación Preclínica de Medicamentos , Sustancias Macromoleculares , Ratones , Proteínas de Neoplasias/biosíntesis , ARN Neoplásico/biosíntesis , Virus Rauscher/efectos de los fármacosRESUMEN
The therapeutic activity of narcissus alkaloid pretazettine HC1 (PTZ) on established Rauscher leukemia has been demonstrated and compared with the isomer tazettine (TZ) and an antibiotic, streptonigrin (SN). PTZ and SN showed remarkable prolongation effect on the life span of the leukemic mice and the antiviral activity has been confirmed in mouse 3T3 cells infected with Rauscher virus. TZ showed no significant activity in the leukemic mice and was inhibitory to the virus growth in the cells at much higher doses than PTZ. It is suggested that the stereochemical rearrangement from PTZ to TZ inactivates the biological activity of PTZ.
Asunto(s)
Alcaloides/uso terapéutico , Leucemia Experimental/tratamiento farmacológico , Alcaloides/farmacología , Alcaloides de Amaryllidaceae , Animales , Línea Celular , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Plantas Medicinales , Virus Rauscher/efectos de los fármacos , Estreptonigrina/farmacología , Estreptonigrina/uso terapéutico , Relación Estructura-ActividadRESUMEN
Mice exposed to selenium-supplemented or -deficient rations were inoculated with an oncogenic virus, Rauscher leukemia virus (RLV), Splenic lesions were not altered by dietary selenium supplementation or depletion. It is concluded that selenium does not affect neoplasia induced by RLV in mice.
Asunto(s)
Neoplasias Experimentales/etiología , Virus Rauscher , Selenio/farmacología , Infecciones Tumorales por Virus/etiología , Animales , Peso Corporal/efectos de los fármacos , Dieta , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/patología , Tamaño de los Órganos/efectos de los fármacos , Selenio/deficiencia , Factores de Tiempo , Infecciones Tumorales por Virus/patologíaRESUMEN
Revistin, a substance that strongly inhibits the reverse transcriptase activity of murine leukemia virus in our screening system, was obtained from a cultured broth of a soil streptomyces which was closely related to Streptomyces filipinensis. The assay method for the activity was based on the inhibition by a test material of the incorporation of 3H-dTMP into DNA synthesized by the reverse transcriptase of an oncogenic RNA virus. Crude revistin was isolated by serial procedures of salting out with ammonium sulfate and precipitation with cetylpyridinium chloride. The crude material showed neither antibacterial nor antifungal activity. It exhibited against splenomegaly in mice caused by Rauscher leukemia virus infection.
Asunto(s)
Virus Rauscher/enzimología , Inhibidores de la Transcriptasa Inversa , Animales , Técnicas Bacteriológicas , ADN Viral/biosíntesis , Evaluación Preclínica de Medicamentos , Virus de la Leucemia Murina/enzimología , Leucemia Experimental/complicaciones , Leucemia Experimental/tratamiento farmacológico , Masculino , Ratones , Esplenomegalia/etiología , Streptomyces/análisis , Streptomyces/citología , Factores de TiempoRESUMEN
The therapeutic activity of the narcissus residual alkaloid A-2 against Rauscher leukemia has been compared with 10 standard anticancer drugs, and synergistic or additive combination pairs have been selected using a viral leukemia and two transplantable tumor systems. An increased beneficial effect has been demonstrated by a combination of the alkylating and DNA-binding agents and the alkaloid against the three malignant tumors, while a beneficial effect by combining the alkaloid and the antimetabolites (either 6-MP or 5-azacytidine) was seen only against the viral leukemia. The alkaloid has no suppressive activity against cellular immunity as tested by PHA reactivity and allogeneic tumor rejection systems.