Pregnancy-specific beta 1-glycoprotein (PS-1), one of a large family in oncofetal antigens, and oncoprecipitin A, a specific glycoprotein isolated from ascidians, have been shown to reduce cell proliferative activity in HeLa-M cells but almost not to change RNA synthesis. Using scanning electron microscopy, distinct surface transductions in the studied cells were demonstrated. After the incubation of cells with oncoprecipitin A, cell shape alteration and intensive cell spreading were observed. The treatment of tumor cells with PS-1 changed cell shape and essentially reduced cell contacts, as compared to control cells. The changes in cell surface and shape correlated with essential reorganization of actin microfilaments. The use of substances influencing the growth and adhesive characteristics of tumor cells may help in understanding mechanisms of cell transformation.

Using the Ehrlich ascite carcinoma cells, exposed to oxidative stress, heat shock, cytochalasin B, vinblastine, Triton X-100 and energy starvation, morphological changes, DNA degradation, and form of cell death were investigated. A rather clear specificity of cell morphology, characteristic of apoptosis, was revealed for the most of treatments, including membrane blebs, chromatin condensation and apoptotic body formation. Karyorhexis was not common for the examined cells. After energy starvation, oxidative stress, heat shock and Triton X-100 treatment, the apoptotic cells were seen to undergo secondary necrosis rather soon; this was not the case after cytochalasin B or vinblastine treatments. In cells exposed to heat shock, cellular pyknosis was frequently developed. Such cells did not undergo secondary necrosis for a long time. The DNA degradation in cells occurred in chaotic manner (without ladder pattern). The fraction of degraded DNA corresponded to that of cells undergoing secondary necrosis.

Common molecular and cellular targets for alkaloids sanguinarine and ellipticine, isolated from well-known antitumor plants (as well as from their various natural and synthetic derivatives), have been studied and described. Sanguinarine and ellipticine are characterized by significant biological activities including a high antitumor potential. Among the important targets of their action the following are to be noted. 1. DNA and other double helical polynucleotides. Due to the ability of DNA-intercalation sanguinarine, ellipticine and some of their derivatives can modify the double helical structures and topological forms of polynucleotides. The results of these modifications in intercalative complexes manifest themselves in the inhibition of numerous enzymatic reactions, dependent on the structures and topological forms of DNA and other polynucleotides. 2. ATP synthesis in mitochondria. Most of DNA-intercalators, including sanguinarine and ellipticine, belong to a group of penetrating (hydrophobic) cations, which are accumulated near the external side of inner mitochondrial membranes during the membrane energization. They neutralize negative charges, arising just as the inner mitochondrial membranes become energized. By this neutralization of membrane charges the ATP synthesis in inhibited and the oxidative phosphorylation renders to be uncoupled. All studied DNA-intercalators under certain conditions uncouple the mitochondrial oxidative phosphorylation. Apparent correlation between the agents' ability for DNA-intercalation and for mitochondrial ATP synthesis inhibition seems to be determined by the importance for both types of reactions of molecule hydrophobicity and positive charges. 3. Cholinesterase systems. Sanguinarine, ellipticine and some of their derivatives, like other DNA-intercalators studied, inhibit also the enzymatic activities of cholinesterase systems due to hydrophobicity and positive charges of their molecules. 4. Sanguinarine (and chelerythrine), are also capable of inhibiting the biological activity of SH-dependent enzymes and proteins. Due to the reactivity of iminium groups in sanguinarine and chelerythrine molecules with nucleophilic reagents, e.g. thiol groups of enzymes and other proteins, the activities of SH-enzymes and proteins are inhibited. In particular, sanguinarine and chelerythrine inhibit enzymatic activity of some SH-dependent ATPases, including membrane-bound cation-transport ATPases. The earlier accumulated experience of the application in medicine of plant saps and extracts containing these alkaloids, and of the treatment of many diseases (including benign and malignant tumors) by isolated alkaloids may be explained, to a certain extent, by the inhibition of activities of the above mentioned cellular targets. The selective toxicity of these alkaloids for the number of transformed cells can be explained in the same manner.

Radiosensitizer AK-2123, a triazol, has been shown to significantly inhibit the development of hepatic metastases induced in syngeneic mice by intrasplenic injections with cels of bowel adenocarcinoma. The antimetastatic effect was produced by use of a very low dose of the drug. A therapeutic dose of AK-2123 has been shown to inhibit active transport of calcium ions across sarcoplasmic reticular cells effected by Ca(2+)-dependent Mg(2+)-activated ATPase. It is suggested that the antimetastatic effect of AK-2123 is determined by at least partial inhibition of active transport of calcium.

Local and distant hemopoietic regulatory mechanisms were studied under various emergencies (immobilization, cytostatic injection, radiation, etc.). There were common processes (cell migration, destruction, T-lymphocyte accumulation, activation of the microenvironment and hemopoietic precursors) forming the local basis for compensatory and adaptive reactions of bone marrow hemopoietic tissue. Emphasis is laid on the association of local mechanisms with the neuroendocrine system which inevitably becomes activated under extreme exposures. On exposure to irritants having no myeloinhibitory effect, neurotransmitters and hormones, mainly glucocorticoids and catecholamines cause the development of erythro- and granulocytopoietic hyperplasia due to stimulation of the hemopoiesis-inducing microenvironment (HIM). Under hemopoiesis-suppressing influences, catecholamine-induced activations of HIM's resistant elements is accompanied by simultaneous inhibition of hemopoietic cells and HIN's factors damaged by an irritant. Under these conditions hemopoietic separation caused by the heterogeneous effect of transmitters on the cell leads to imbalance of hemopoietic precursor proliferation and differentiation and, finally, to delayed hemopoietic tissue regeneration. At the same time, the neuroendocrine system does not seem to play a leading role as compared to the control intact hemopoiesis.

The effect of calcium gluconate on the toxicity of the anthracycline antibiotic doxorubicin (DOX) in mice was studied. Calcium gluconate showed a significant protective action with respect to the DOX acute toxicity. When DOX was used in the lethal doses, up to the LD50s calcium gluconate protected all the mice from death. At the DOX LD100 or higher the antitoxic effect of calcium gluconate manifested itself in a lower death rate and/or in a higher lifespan of the animals (at least 2-fold). When DOX was used for the treatment course its chronic toxicity in the presence of calcium gluconate was 2 or more times lower by all the quantitative indices: the lifespan of the animals that died, the maximum and minimum total lethal doses of DOX, the latent period before the first mouse death, the overall duration of the DOX treatment course. The antitoxic effect of calcium gluconate also manifested itself in a lower DOX acute and chronic toxicity with respect to the gastrointestinal tract. Thus, calcium gluconate proved to be an effective DOX antitoxic modificator which provided the use of about 2 times higher single and courses doses of DOX in mice.

In the series of glycidylic ethers of alkylophosphoric and methylphosphoric acids three types of compounds have been identified: those possessing anticholinesterase, narcotic, and antineoplastic activity. Monoglycidylic ethers of diethyl- and diisopropylphosphoric acids and diglycidylic ether of ethylphosphoric acid caused intoxication of animals with the cholinergic excitation syndrome, and in vitro in a concentration of 1 mmol/liter strongly inhibited cholinesterase, stimulated the motor activity of an intestinal segment, but did not demonstrate cytotoxic activity in relation to NK/Ly strain tumor cells. Monoglycidylic ethers of di-n-propyl-, di-iso-butyl, and di-n-butyl-phosphoric acids as well as diglycidylic ethers of n-butyl- and iso-amylphosphoric acids caused a "hypnotic state" in the animals, suppressed the motor activity of an isolated intestinal segment, considerably increased the number of diffusely stained by Aĭzenman's [correction of Aisenmanns'] method cells of ascitic NK/Ly tumor in vitro, but poorly inhibited the growth of this tumor in chemotherapeutic experiments. Diglycidylic ethers of methyl-, n-propyl-, iso-butylphosphoric, and methylphosphonic acids caused poisoning of the type of intoxication by alkylating agents, weakly influenced cholinesterase activity, did not change the character of contractions of the intestinal segment. In vitro they caused a strong cytotoxic effect, but delayed the growth of the NK/Ly tumor treated animals by 84-100%. The possibility of the phosphororganic epoxides under study taking part in the reactions of alkylation and phosphorylation is suggested.

The genetic (mutagenic) activity of ultralow doses (below 1 x 10(-12)M of the antitumor antibiotics, anthracyclines and bleomycin, as well as the typical pollutant and component of the urban atmosphere 2-nitrofluorene, was studied on the model of Salmonella typhimurium LT2 TA98 his D3052. It was shown for the first time that carminomycin and 2-nitrofluorene at 1 x 10(-17) and 1 x 10(-22) M induced a two- to threefold increase in the number of revertants-prototrophs over the spontaneous background. The areas of increase (1 x 10(-15) M) and decrease (1 x 10(-19) and 1 x 10(-21) M) in the number of mutants, as compared with the spontaneous background, were found in the curve of dose dependence of the number of mutants in the presence of bleomycin. The results obtained were discussed in terms of their ecological importance.

A mathematical model is proposed for the description of the cytostatic effects of the chelating agents of the transition metal ions on cell cultures. Chelate complexes of picolinic acid and bivalent iron ions, which play an important role in nucleic acid synthesis, were considered as an example. Kinetic equations of the theory of receptors were used for model construction. The best correspondence with the experimental dose-effect curves, obtained in the experiments on influence of various picolinic acid concentrations on division of the SPEV cultured cells, is provided by the model of threshold type. The parameters lying in the basis of the theory of receptors and relating the biological effect (cell division) to the number of ligand-receptor complexes were calculated.

Studying the action of the two antitumour platinum compounds--cisplatin capable of exerting a nephrotoxic action and cycloplatam which has no damaging effect on the kidney, it was found that 3 h after the administration of cycloplatam the content of platinum in the kidney was 2 times lower than in the cfse of cisplatin. Due to different dynamics of the excretion of platinum compounds from the kidney 5 lays after their addition the content of platinum in the kidney was the same in both cases. The content of platinum in the nuclei, mitochondria and supernatant with respect to a total content in the kidney cortex was almost equal for both compounds. Inhibition of nephrotoxic effect of cisplatin after the animals were pretreated with choline chloride or paraaminohippurate is not connected with a decrease of platinum in the kidney either 3 h, or 5 days after the injection of these preparations. The mechanisms of nephrotoxic action of cisplatin and its prevention are discussed.

Carotenoids are shown to inhibit the initiation phase of carcinogenesis due to their antioxidant activity. But neither antioxidant nor pro-vitamin properties of these pigments can explain their antitumor action in many cases. Studying this problem another property of carotenoids must be accounted: their ability to modify biomembranes reinforcing lipid bilayer and decreasing its fluidity. High level of membrane fluidity is characteristic of the tumor cells and they are very sensitive to its decrease. Suppressing of membrane fluidity is the mechanism for anticancer action of tamoxifen-related compounds, and there are strong reasons to suggest the same mechanism for carotenoids.

Modern literary data about the treatment of myelodysplastic syndromes are reviewed. There have been analysed traditional methods and recent scientific achievements, such as using of the colony-stimulating growth factors and bone marrow transplantation.

A synthesis of 3-(1H-3-indolyl)-4-(1-glycosyl-3-indolyl)furan-2,5-diones and -1H-pyrrole-2,5-diones modified with the residues of D-ribo-, D-xylo-, L-arabino-, D-galactopyranose, and D-lactose was described. Influence of the compounds prepared on DNA biosynthesis in CaOv cells was studied.