RESUMEN
A purpose of this research is the study of spontaneous cytotoxic activity of effector cells (EC) of the innate immunity of animals against target cells (TC) of cultured hepatoma. There are established differences in the cytotoxic potential of freshly non-activated mouse and rat splenocytes: TC exhibit resistance to splenocytes of mice C3HA and are exposed to active dose-dependent killing under the influence of splenocytes outbred rats. There were revealed two mechanisms of killing of clip-target by splenocytes of rats--secretory variant (Zajdel hepatoma) and the path of classical apoptosis (hepatomas HTC, MH-22a and BWTG3). Single intraperitoneal administration of anticancer drugs cyclophosphamide (CP) and 5-fluorouracil (5-FU) to animals inhibits secretory pathway, whereas the activity of the apoptotic mechanism is enhanced after administration of CF to animals and is unchanged under the action of 5-FU.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Citotoxicidad Inmunológica/efectos de los fármacos , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Bazo/inmunología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Línea Celular Tumoral , Ciclofosfamida/farmacología , Fluorouracilo/farmacología , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos C3H , Ratas , Bazo/citología , Bazo/efectos de los fármacosRESUMEN
This study examines the immunomodulating effect of cytostatic drug--cyclophosphamide (Cy)--on natural cytotoxic activity of rats and mice splenocytes. The cytotoxicity of the effector cells against the confluent monolayer cell lines of rat hepatoma Zajdela and HTC and mice hepatoma MH-22a was estimated by means the morphometric analysis. It was shown, that 48 h after single intraperitoneal injection of Cy produced a immunomodulating effect on the activity of splenocytes--suppressor action on cells of Zajdela hepatoma and immunopotentiating action on the target cells of HTC and MH-22a hepatomas. The possible mechanisms of immunopotentiating effect of Cy are discussed.
Asunto(s)
Apoptosis/efectos de los fármacos , Ciclofosfamida/farmacología , Inmunomodulación/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Bazo/inmunología , Linfocitos T/efectos de los fármacos , Animales , Apoptosis/inmunología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Pruebas Inmunológicas de Citotoxicidad , Citotoxicidad Inmunológica/efectos de los fármacos , Procesamiento de Imagen Asistido por Computador , Factores Inmunológicos/farmacología , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/terapia , Masculino , Ratones , Ratones Endogámicos C3H , Microscopía , Especificidad de Órganos , Cultivo Primario de Células , Ratas , Bazo/citología , Bazo/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
The present study was aimed to examine the possibility to use of the morphometric analysis for estimation of the total natural cytotoxic activity of rat and mice C3HA splenocytes against the cultured target cells which formed confluent monolayers. By means of this method we have revealed that two rat monolayer hepatoma cell lines -- HTC and Zajdela -- were sensitive to cytolysis mediated by rat effector cells, but not splenocytes of C3HA mice. The mild pretreatment with 0.5% paraformaldehyde of the rat splenocytes produced a significant decrease only in the cytotoxic activity against the target cells line Zajdela and don't affect the lysis of the other target HTC cells. These results suggest that the natural cytotoxic rat cells may mediate their lytic functions toward tested target lines by different ways. In the case of HTC cells as the targets the effectors induce death receptor-mediated apoptosis, as to target cells Zajdela they deliver lethal hit by perforin-granzyme exocytosis mechanism. The cultured cell monolayers of mice hepatoma -- MH-22a and BWTG3 -- cells showed under conditions of our experiments the resistance to cytolysis by homological effector cells; however, the hepatoma MH-22a cells were susceptible to killing mediated by rat cytotoxic splenocytes.
Asunto(s)
Carcinoma Hepatocelular/inmunología , Citotoxicidad Inmunológica , Linfocitos/inmunología , Bazo/inmunología , Animales , Apoptosis/inmunología , Línea Celular Tumoral , Exocitosis/inmunología , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Perforina/metabolismo , Fotomicrografía , RatasRESUMEN
In the course of malignant growth processes in patients with lung cancer, a decrease of natural cytotoxic activity of peripheral blood lymphocytes was observed. This process was accompanied by changes of activities of two lysosomal enzymes, arylsulfatase and acid phosphatase, suggesting participation of these enzymes in manifestation of effector functions of lymphocytes in cancer patients. The level of activity of granular enzyme, beta-glucuronidase, remained unchanged at all stages of disease. A study of natural killer activity of C3HA mice splenocytes after inoculation of transplantable hepatoma 22-a cells revealed a relative stability of the level of their cytotoxicity, and of the activities of lysosomal enzymes--arylsulfatase, acid phosphatase, alpha-mannosidase, acid lipase, N-acetyl-beta-D-glucosidase, and beta-galactosidase, beginning from the 3rd day after hepatoma implantation.
Asunto(s)
Células Asesinas Naturales/inmunología , Neoplasias Hepáticas Experimentales/inmunología , Bazo/inmunología , Fosfatasa Ácida/análisis , Fosfatasa Ácida/metabolismo , Animales , Arilsulfatasas/análisis , Arilsulfatasas/metabolismo , Gránulos Citoplasmáticos/enzimología , Citotoxicidad Inmunológica , Humanos , Células Asesinas Naturales/enzimología , Neoplasias Hepáticas Experimentales/enzimología , Neoplasias Hepáticas Experimentales/patología , Ratones , Ratones Endogámicos C3H , Estadificación de Neoplasias , Bazo/citología , Bazo/enzimologíaRESUMEN
Effects of two immunosuppressors, cyclophosphane abd 5-fluorouracyl, used in clinical practice for treatment of oncological diseases, were assessed in respect to cytotoxicity and activity of several lysosomal enzymes located in splenocyte granules of C3HA mice. 48 h after a single intraperitoneal injection, both preparations produced a marked decrease in their cytotoxic activity, which was accompanied by a pronounced splenopathy. Both preparations were shown to decrease activity of arylsulfatase. Administration of cyclophosphane brought about the rise of activity of acid lipase as compared to control. Activities of acid phosphatase, alpha-mannosidase, beta-galactosidase, and N-acetyl-beta-D-glucosidase did not change after administration of the used immunosuppressors. It may be suggested that only arylsulfatase and acid lipase are involved in performance and(or) manifestation of the natural killer activity in splenocytes of the C3HA mice after their administration with cyclophosphane or 5-fluorouracyl.
Asunto(s)
Citotoxicidad Inmunológica/efectos de los fármacos , Inmunosupresores/farmacología , Lisosomas/enzimología , Bazo/efectos de los fármacos , Animales , Arilsulfatasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Ciclofosfamida/farmacología , Fluorouracilo/farmacología , Inyecciones Intraperitoneales , Lipasa/metabolismo , Masculino , Ratones , Ratones Endogámicos C3H , Bazo/citología , Bazo/inmunología , Células Tumorales CultivadasRESUMEN
The cytotoxic activity of peripheral blood lymphocytes of 135 lung cancer patients was studied. A wide range of cytotoxicity values was shown--from 0 to 88%. During the randomized investigation of these patients no strong correlation was found between the levels of cytotoxicity and the cancer stages. A certain tendency of increasing the number of patients with weak cytotoxic activity upon progressing disease was followed. The lymphocytes with a strong natural killer activity did not react on the in vitro incubation with interleukin-2. The lymphocytes with a strong was obtained when the lymphocytes with the lowest cytotoxicity levels were incubated with this immunomodulator.
Asunto(s)
Interleucina-2/farmacología , Neoplasias Pulmonares/inmunología , Linfocitos/efectos de los fármacos , Células Cultivadas , Medios de Cultivo , Pruebas Inmunológicas de Citotoxicidad/métodos , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Linfocitos/inmunología , Distribución Aleatoria , Proteínas Recombinantes/farmacologíaRESUMEN
The immunogenicity of the Coxiella burnetii corpuscle antigen and two its components, obtained after the treatment with chloroform-methanol or extraction by trichloroacetic acid, was investigated. All the studied antigens were highly immunogenic. A strong correlation was discovered between the immunogenic and immunomodulating properties of the C. burnetii antigens. Cells of the mononuclear phagocytic system are the targets for stimulating action of the studied antigens. A cyclic increase of antibacterial activity and oxygen-dependent metabolism of the peritoneal cells was noted, in addition to the increase of the natural splenocyte cytotoxicity caused by the action of these antigens. The role of cytokines in rising the activity of peritoneal cells and splenocytes, caused by immunization of mice with the above antigenic substances, is discussed.
Asunto(s)
Adyuvantes Inmunológicos , Antígenos Bacterianos/inmunología , Coxiella burnetii/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/aislamiento & purificación , Citotoxicidad Inmunológica/inmunología , Inmunización , Interferones/sangre , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C3H , Rickettsia prowazekii/inmunología , Salmonella typhimurium/inmunología , Factores de TiempoRESUMEN
The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II-IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II-IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyond that already available from staging. However, those stage II-IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.
Asunto(s)
Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Anciano , Pruebas Inmunológicas de Citotoxicidad , Citotoxicidad Inmunológica/inmunología , Femenino , Humanos , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/patología , Complejo Mayor de Histocompatibilidad/inmunología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
The role of T-lymphocytes in natural cytotoxicity of splenocytes of C3HA mice after a single injection of 20-methylcholanthrene (20-MC) was investigated. A splenocyte suspension was treated with anti-T-cell serum and complement. This treatment was not shown to exert influence on the natural cytotoxicity of splenocytes within 1-13 days after injecting 20-MC.
Asunto(s)
Suero Antilinfocítico/farmacología , Citotoxicidad Inmunológica/efectos de los fármacos , Metilcolantreno/farmacología , Ratones Endogámicos C3H/inmunología , Bazo/efectos de los fármacos , Linfocitos T/inmunología , Animales , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Masculino , Ratones , Bazo/citología , Bazo/inmunología , Factores de TiempoRESUMEN
Coxiella burnetii antigens stimulate the defence against growth of hepatoma 22a cells. The antigen-stimulated mice survived longer, they considerably later developed palpable tumours and showed a retarded tumour growth. The enhanced resistance to tumour growth may be explained by at least 2 interrelated phenomena; namely by the induction of interferon-like activity and an increased NK cell activity.
Asunto(s)
Adyuvantes Inmunológicos , Antígenos Bacterianos/administración & dosificación , Coxiella/inmunología , Neoplasias Hepáticas Experimentales/terapia , Animales , Inmunoterapia , Interferones/biosíntesis , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas Experimentales/inmunología , Ratones , Ratones Endogámicos C3HRESUMEN
The influence of macrophages on NK cell activity of C3HA mice on 1, 7 and 13 days after single i. m. injection of 20-methylcholanthren was investigated. It is shown that macrophages significantly stimulate this activity on the 13th day after carcinogen application.
Asunto(s)
Células Asesinas Naturales/inmunología , Macrófagos/inmunología , Metilcolantreno/toxicidad , Neoplasias Experimentales/inmunología , Bazo/inmunología , Animales , Adhesión Celular/inmunología , Células Cultivadas/inmunología , Pruebas Inmunológicas de Citotoxicidad , Masculino , Ratones , Ratones Endogámicos C3H , Neoplasias Experimentales/inducido químicamente , Factores de TiempoRESUMEN
The induction of tumor in C3HA mice after intramuscular injection with 20-methylcholanthrene is accompanied by a decrease in natural antitumor resistance. This conclusion is based on the observation of the decreased natural killer activity per total number of splenocytes, from the time of carcinogen application till the appearance of tumor nodes.
Asunto(s)
Células Asesinas Naturales/efectos de los fármacos , Metilcolantreno/toxicidad , Ratones Endogámicos C3H/inmunología , Neoplasias Experimentales/inducido químicamente , Bazo/efectos de los fármacos , Animales , Recuento de Células/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/inmunología , Masculino , Ratones , Neoplasias Experimentales/inmunología , Tamaño de los Órganos/efectos de los fármacos , Bazo/inmunología , Factores de TiempoRESUMEN
Immunization of C3HA mice with homogenate of normal syngeneic liver at a dosage causing elevation of antitumor resistance damages the liver of recipients. The damage involves the formation of foci of necrosis and the alteration in activities of some tissue specific and embryonal enzymes. The damage is reversible; its degree and the rate of reverse depends on a dosage of homogenate injected.
Asunto(s)
Inmunización/métodos , Hígado/fisiopatología , Ratones Endogámicos C3H/fisiología , Animales , Relación Dosis-Respuesta Inmunológica , Inmunidad , Hígado/enzimología , Hígado/inmunología , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/prevención & control , Pulmón/inmunología , Ratones , Miocardio/inmunología , Necrosis , Trasplante de Neoplasias , Factores de TiempoRESUMEN
Partial hepatectomy leads to both increasing of natural cell-mediated activity and sensibilization level (SL) of splenocytes of hepatectomized mice towards antigens of the syngeneic liver. The wave-like variability of SL was shown with sharp increase at 3, 6 and 9 days after operation. Natural killer activity was elevated on the 2nd and 10th days with a significant decrease on the 3-4th days after operation. It is assumed that the variability in the functional activity of splenocytes under study may characterized splenocytes of different populations.
Asunto(s)
Antígenos/inmunología , Inmunización , Células Asesinas Naturales/inmunología , Hígado/fisiología , Bazo/inmunología , Animales , Citotoxicidad Inmunológica , Hepatectomía , Masculino , Ratones , Ratones Endogámicos C3H , Factores de TiempoRESUMEN
Immunization of C3HA mice with allogeneic tissue (liver of DBA mice) leads to wave-like variability in the natural killer activity of their recipient splenocytes. This variability is similar to that of NK-activity due to syngeneic immunization and is characterized by a sharp increase on days 1, 3-4 and 6 after immunization. Xenogeneic immunization exerts no influence on NK-activity, if compared with the injection of 0.14 M NaCl.
Asunto(s)
Antígenos/inmunología , Inmunización/métodos , Células Asesinas Naturales/inmunología , Animales , Hígado/inmunología , Trasplante de Hígado , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos DBA , Ratas , Bazo/inmunología , Factores de Tiempo , Inmunología del Trasplante , Trasplante Heterólogo , Trasplante HomólogoRESUMEN
Immunization of C3HA mice with homogenized syngeneous liver led to sensibilization of splenocytes towards liver antigens and to the increase in natural killer cell activity towards K-562 cells. The dynamics of sensibilization and cytotoxicity in different time intervals after immunization has led to a conclusion about a correlation between the two above phenomena.
Asunto(s)
Antígenos/inmunología , Inmunización/métodos , Células Asesinas Naturales/inmunología , Bazo/inmunología , Animales , Pruebas Inmunológicas de Citotoxicidad , Pruebas de Fijación de Látex , Hígado/inmunología , Trasplante de Hígado , Masculino , Ratones , Ratones Endogámicos C3H , Inmunología del Trasplante , Trasplante IsogénicoRESUMEN
Six aromatic amines were studied for their mutagenic activity using Salmonella typhimurium TA 100 and TA 98. 3,3'-dichlorobenzidine, ortho-tolidine, benzidine, 2-naphthylamine proved to be mutagenic, while aminotobias acid and 2,2',4,4'-tetraaminodiphenyl did not show mutagenic activity. Chronic experiments on mice and rats using these compounds revealed a close correlation between carcinogenicity and mutagenicity.
Asunto(s)
2-Naftilamina/toxicidad , Compuestos de Anilina/toxicidad , Bencidinas/toxicidad , Mutágenos , Naftalenos/toxicidad , Neoplasias Experimentales/inducido químicamente , Animales , Ratones , Ratones Endogámicos C57BL , Pruebas de Mutagenicidad , Ratas , Salmonella typhimurium/genéticaRESUMEN
Various fractions of the immune nuclear RNA were isolated from spleens of phage T2 immunized rats. The fractions were compared for their ability to induce anti-phage T2 antibody synthesis in transplantable lymphosarcoma cells. The most active proved to be the nuclear sap RNA and its subfraction with sedimentation constant of 10 S. The 4S and 26S subfractions RNA were less stable and in some experiments failed to induce antibody synthesis.
Asunto(s)
Anticuerpos Antivirales/biosíntesis , Comunicación Celular , Núcleo Celular/inmunología , Linfoma no Hodgkin/inmunología , ARN Neoplásico/inmunología , Fagos T/inmunología , Animales , Inmunización , ARN Neoplásico/aislamiento & purificación , Ratas , Bazo/inmunología , TemperaturaRESUMEN
It has been proved that nuclear and cytoplasmic RNAs, isolated from spleens of T2 phage immunized rats and mice, can induce T2 phage antibodies in cells of the transplantable rat lymphosarcoma. With the nuclear RNA from rat spleens, the effect is persisting in a number of subsequent cell generations. The data presented are principally in accord with results of the authors' previous studies in which lymphosarcoma cells were treated with RNA extracted from spleens of rat immunized with sheep red cells. These results well compare with the authors' earlier advanced hypothesis suggesting a possible involvement of RNA in deblockation of genes responsible for the synthesis of the antibodies in question.
Asunto(s)
Anticuerpos Antivirales/biosíntesis , Formación de Anticuerpos , Colifagos/inmunología , Inmunidad Celular , Inmunidad Materno-Adquirida , Linfoma no Hodgkin/inmunología , ARN/inmunología , Bazo/inmunología , Animales , Anticuerpos Antineoplásicos/biosíntesis , Bacteriólisis , Escherichia coli , Inmunización , Ratones , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Ratas , Factores de TiempoRESUMEN
An attempt to induce some forward and back mutations in two Escherichia coli strains (his- and HfrH requiring thiamine) under the action of the carcinogenic nitrosamines--dimethylnitrosamine (DMN) and diethylnitrosamine (DEN)--is described. For this purpose the cells of E. coli were treated with 5% DMN or 1% DEN for 1 hour at 37 degrees C in 0.14 M NaCl. It was shown that the sensitivity of both strains to both nitrose compounds was not the same. DEN was 5-fold as toxic as DMN for the E. coli cells. DMN and DEN induced neither mutations of resistance to 10(-3) M valine, nor reversions in histidine-dependent strain. These mutations were obtained after the cells were treated with 0.1 M NaNO2. Lethal effects of DMN increased more than in 5 times and the toxicity of DEN did not change in hydroxylating mixture, in which nitrosamines derived to active compounds. Under these conditions both carcinogenes showed a mutagenic activity. DEN proved to be about twice as strong mutagenically as DMN. Thus, in our experiments we could see that DMN and DEN could induce both forward and back mutations in E. coli.