Effect of Chemically Transformed Macrocyclic Polyene Antibiotics on Tumor Cells.

Comparative analysis of the effects of chemically transformed polyene antibiotics pimaricin, nystatin, lucensomycin, amphotericin B, and levorin on biological objects in vivo and in vitro revealed the greatest biological activity of original amphotericin B and levorin with its derivatives. The study also examined the effects of alkyl derivatives of amphotericin B and levorin modified in certain parts of the lactone ring on the lipid and biological membranes. It is established that methylated levorin possesses larger biological activity than the original antibiotic. Examination of the effects of alkyl derivatives of levorin and amphotericin B on cell cultures C6 (rat glioma) and HeLa (human cervical carcinoma) in vitro revealed the antitumor action of methylated levorin and original amphotericin B.

[Red blood cells hemolysis under combined action of ultrasonic waves and polyene antibiotics].

Ultrasonic and induced hemolysis of red blood cells in the presence of alkyl derivatives of amphotericin B and levorin modified by the amino and carboxy groups was investigated. Amphotericin B derivatives such as metamphocin, ethamphocin and carboamphocin and levorin derivatives such as levoridon, isolevoridon and carbolevoridon were shown to have their own hemolytic activity in isotonic medium at concentrations of 10(-5) - 10(-4) M in erythrocyte suspension. The exposure of erythromycytes to pure dimethylsulfoxide (0.1-30%), the main solvent of polyene antibiotics, as well as to propamphocin and butamphocin did not induce hemolysis and had a stabilizing action an red blood cells during the ultrasonic hemolysis. It was suggested that changing of the mechanical strength of erythrocytes under the action of the polyenes was likely associated with impairment of microviscosity of the protein-lipid system of the erythrocyte membranes due to formation of structural ionic channels of molecular size.

[Hemolytic resistance of erythrocytes in the development of experimental tumors]. / Gemoliticheskaia ustoichivost' éritrotsitov pri razvitii éksperimental'nykh opukholei.

Peculiarities of variations in the mechanical resistance of erythrocytes from mice with tumours were studied depending on the growth stage of tumours (lymphoma NK/Ly and sarcoma S-37). The accumulation of erythrocytes with the increased mechanical resistance at the stage of rapid tumour development (on the 4 to 6th days) was revealed by the kinetic method of ultrasonic haemolysis. Quantitative parameters of ultrasonic haemolytic resistance of erythrocytes from normal and tumour-bearing mice were used as criteria for the red blood cell changes depending on the cell age in blood. The increase of haemolytic resistance at the rapid stage of tumour growth may be caused by a higher number of "young" erythrocytes in blood. Ultrasonic haemolytic resistance increases when there is no changes in the erythrocyte quantity and hemoglobin concentration. The kinetic study of ultrasonic haemolysis of the erythrocytes isolated from peripheric blood permits estimating the reaction of the blood forming organs to the origin and development of tumours.

[Effect of chlorine-containing pesticides on the hemolytic stability and acetylcholinesterase activity of erythrocytes]. / Vliianie nekotorykh khlorsoderzhashchikh pestitsidov na gemoliticheskuiu ustoichivost' i atsetilkholinésteraznuiu aktivnost' éritrotsitov.

The hemolytic action of the chlorine-containing pesticides, trichloroacetic acid (TCA), pentachlorophenolate (PCP), chlorophos and pentachloronitrobenzene (PCNB) on red cells was studied, as were their effects on acetylcholinesterase activity and resistance of red cells to mechanical hemolysis by ultrasound. The modifying action of pesticides on red cell membranes was shown to lead to their mechanical resistance. TCA, PCP and chlorophos were found to sensitize red cells whereas PCNB to make them resistant to the mechanical action of ultrasound. The kinetic characteristics of the structural functional disorders of red cells might be used as quantitative criteria of the efficacy of the action of pesticides on the cells.

[Ultrasonic hemolysis of normal and pathological erythrocytes]. / Izuchenie ul'trazvukovogo gemoliza éritrotsitov v norme i pri patologii.

The kinetic method of the investigation of erythrocyte haemolysis normal and at different tumour pathologies by ultrasound was developed. The quantitative parameters of the mechanical resistance of erythrocytes were studied (time and velocity of haemolysis, time of half-destruction, the distribution of erythrocytes by their haemolytic resistance). The studied parameters differ between the normal state and the tumour in organism. The analysis of the differential distribution of erythrocytes by their resistance to ultrasonic haemolysis revealed the occurrence in the patient's blood of erythrocytes with increased resistance ("young" erythrocytes). The mechanical resistance of the erythrocytes at pathology was shown to increase as compared with the normal state. The differences in the effective constants of ultrasonic haemolysis velocity were estimated for the normal state and for different tumours. They are caused by the changes in visco-elastic properties of red blood cells.