RESUMEN
The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.
Asunto(s)
Carcinoma Pulmonar de Lewis/metabolismo , Metabolismo Energético/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sarcoma 37/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patología , Catalasa/genética , Catalasa/metabolismo , Ácido Dicloroacético/farmacología , Metabolismo Energético/genética , Humanos , Ratones , Mitocondrias/genética , Mitocondrias/patología , Especificidad de Órganos , Estrés Oxidativo , Sarcoma 37/tratamiento farmacológico , Sarcoma 37/genética , Sarcoma 37/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
The damaging effects on the structure of a supramolecular DNA complex of sarcoma-37 cells in mice following the use of the therapeutic doses of khanerol were found. Capillary elastoviscosimetry and nucleoid sedimentation procedure showed that the damage of the supramolecular DNA complex structure becomes apparent already after 4 hours, and increases by 24 hour. In studies of the binding of khanerol with DNA by Cd and Tmelt. the procedure showed direct interaction of khanerol with DNA. The role of conformational changes of the supramolecular DNA complex in the cytotoxic action of antitumour agents is discussed.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , ADN de Neoplasias/efectos de los fármacos , ADN Superhelicoidal/efectos de los fármacos , Sarcoma 37/tratamiento farmacológico , Sarcoma Experimental/tratamiento farmacológico , Animales , Dicroismo Circular , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Ratones , Ratones Endogámicos , Trasplante de Neoplasias , Fenoles , Sarcoma 37/genética , Factores de Tiempo , ViscosidadRESUMEN
By C-method of chromosome staining three transplantable murine tumor lines passaged in vivo were studied. Marker chromosomes were discovered in all cell lines under observation. The previously described marker chromosomes B and C were found in transplantable Ehrlich ascites carcinoma cells, acrocentric chromosome with additional C-band --in cells of line C-37, acrocentric chromosome with double quantity of subcentrometric heterochromatin in cells of line TG-180. The data obtained make it possible to distinguish the lines under study by C-method of chromosome staining.