Asterin is a novel antitumor antibiotic isolated from a medicinal plant of the aster family in the Department of Antibiotics of the Institute of Microbiology and Virology of the National Academy of Sciences of the Ukraine. The mechanisms of its influence on the host antitumor resistance were studied. Asterin was shown to promote the modulation of the specific and nonspecific link of the antitumor resistance. It activated to a definite extent the effector productive phase with the dominating influence on the proliferative phase. The antibiotic immunocorrective action was achieved via the recovery of the suppression mechanism controlling the proliferation and differentiation of all the cell populations. The molecular mechanisms of the asterin action on the lymphocyte transformation characterized by an increase in the metabolism and synthesis of the membrane phospholipids are likely associated with the control of their free radical processes.

Bleomycetin, an antitumor antibiotic of the domestic origin, is component A5 of the bleomycin complex. Design of new drug delivery systems especially for local application is an important problem of antitumor chemotherapy. Bleomycetin immobilized on ion exchange medical gauze was studied with this purpose in an in vivo experimental model of murine lympholeukemia NK/Ly. Subcutaneous implantation of the new dosage form of bleomycetin with prolonged action provided a significant antitumor systemic effect evident from an increase in the mouse life-span. In vitro determination of the bleomycetin contents in the gauze revealed that the antibiotic was completely absorbed from the carrier within 72 hours. The bleomycetin half-life in the plasma after the antibiotic administration in the bound form on the ion exchange gauze was twice as long as that after the antibiotic injection with NaCl isotonic solution.

Cyclophosphamide administration to pregnant mice results in germ cells reduction in their progeny. Dynamics of follicular growth initiation was studied in these conditions. Results of the investigation confirmed the presence of dependence between the level of follicular growth and the size of the quiescent pool. This dependence was found to be non-linear-two threshold areas of values for the germ cell number with the changing dependence were discovered. The contribution of growing follicles tends to increase as the entire germinative population reduces in size. Increase of the share of growing follicles correlates with the increase of the ovarian stroma relative volume. This allows to suggest the possibility of participation of the latter in the regulation of follicular growth initiation.

Antitumor and cytotoxic activity of monoglucosides such as 3-0-panaxadiol (1), 12-0-panaxadiol (2) and 20-0-panaxadiol (3) and 3-0-betulafolientriol (4), 12-0-betulafolientriol (5) and 20-0-betulafolientriol (6) was studied. It was found that in concentrations of 10 to 50 micrograms/ml the above monosides induced marked impairment of the selective permeability of the tumor cells and the inhibition of the labeled precursor inclusion into the macromolecule biosynthesis. Administration of the monosides in a single dose of 100 mg/kg 24 hours after the inoculation of the Ehrlich tumor cells resulted in prolongation of the mean life-span of the mice by 144 per cent (1), 153 per cent (2), 144 per cent (3), 125 per cent (4), 133 per cent (5) and 178 per cent (6). A significant reduction of the tumor mass was observed at the early stages of the tumor development and later the tumor progress intensively resumed. The tests for the effect of the monoside-activated macrophages on the growth of the tumor cells showed that production of the growth factors by the macrophages was stable and had a negative action on the efficacy of the chemotherapy with the monoglucosides.

The review covers recent data on the use of mycelial fungi for the production of carotenoids and on the chemical composition and biological functions of micromycete carotenoids. Particular emphasis is placed on the physiology and biochemical characteristics of the mucor fungus Blakeslea trispora, the only beta-carotene producer employed on an industrial scale. The biotechnological importance of the fungus with respect to lycopene production, recent data on the high antioxidant activity of lycopene, and potential applications of carotenoids in medicine are discussed.

The features of antimitotic substances as radioprotectors were studied. In vitro experiments have demonstrated that taxol revealed radioprotective features concerning the process of polymerization of irradiated microtubules. These results were the basis for the use of taxol and some other substances with high affinity for cytoskeleton proteins as potential radiomodificators in vivo. Experiments with cultivated fibroblasts revealed that colchicine significantly enhances radioactive injuries of cells while taxol and phalloidin manifest their radioprotective features.

The antiemetogenic effect of navoban (Sandoz) was studied in 26 patients receiving chemotherapy, with application of platidiam in 22 cases included. No vomiting was registered. Nausea was observed in 9 cases within the first 24 hrs and a slight reduction in appetite--in 13 cases. Navoban proved one of the most potent antiemetics devoid of any untoward side-effects.

The ability of two-cell minor lipid components: N-palmitoyl- and N-stearoylethanolamines to influence the Lewis lung carcinoma metastases has been studied. It is shown that these compounds decrease the quantity and the volume of metastases. Acyl derivatives of ethanolamine inhibit simultaneously the process of lipid peroxidation. Mice C57 B1/6 were intraperitonealy injected labeled 3H-N-stearoylethanolamine. Localization of this radioactive label in some organs of the animals was studied.

Nine novel chemically modified polyamine analogues were synthesized as potential antitumor agents and evaluated for their capacity to inhibit biosynthesis of polyamines in cell-free system of rat hepatoma G-27. All analogues (numbers I-IX) were used in a final concentration of 10(-4) M. Compounds I-VI modified by adenosine demonstrated activation both ODC activity (except substance I) and polyamine synthesis. The degree of activation depended on the length and quantity of methylene groups in the structure of the analogues. Compound I inhibited ODC activity stronger than its known inhibitor DFMO. On the other hand, substances VII-IX modified by two uracils significantly reduced polyamine levels as well as inhibited the ODC activity more effectively than DFMO. These results indicate that in cell-free system of rat hepatoma G-27 new analogues I and VII-IX are cap able of to some extent inhibiting biosynthesis of polyamines. These drugs might also be useful both as experimental approaches for investigation of peculiarities of polyamine metabolism, and possible application of these substances as antineoplastic agents.

Literary data concerning structure-activity relationships in compounds exhibiting an antipromoter activity in skin tests of full tumour promotion by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or its analogs have been reviewed. Five classes of antipromoters differing in their action on the first and second stages of tumour promotion have been identified, namely: i) 2nd stage promoters/1st stage inhibitors; ii) 1st stage promoters/2nd stage inhibitors; iii) 2nd stage inhibitors; iiii) 1st stage inhibitors; iiiii) 1st and 2nd stage inhibitors. The results on structure-activity of antipromoters were compared with the results of previous studies on phorbol tumour promoters. These data made it possible to determine the reciprocal localization of binding sites for various classes of antipromoters and individual functionally important phorbol fragments on protein kinase C. A new detailed variant of the model of two-center binding of full phorbol tumour promoters on protein kinase C is proposed.

The experimental data concerning the composition of DNA-bound lipids of different eukaryotic and prokaryotic cells have been summarized. Using X-ray diffraction patterns, circular dichroism, microcalorimetry, electron microscopy, viscoelastometry and sedimentation methods, it has been proved that the lipids are important integral components of chromosomal DNA. It was shown that the DNA-bound lipids have a specific composition which differs from that of chromatin, nuclear membrane and matrix lipids. The composition of these lipids changes depending on the activity of the genome and the phase of the cell cycle as well as when DNA passes from a supercoiled into a relaxed state. The DNA of cancer cells has a specific composition of the lipid component. The lipids take part in the regulation of transcription. The DNA-bound lipids are hypersensitive target sites for ionizing radiation and anticancer agents. The role of this lipid class in structure-functional organization of chromosomal DNA is discussed.

An antibiotic complex was extracted from the culture fluid of Streptomyces phaeofaciens, strain 51. By the physicochemical properties it was referred to the group of aureolic acid. The complex was separated to chromatographically pure components by column chromatography. The main component was designated as antibiotic 51-I. Its physicochemical and biological properties were studied. Comparison of the data on the study of antibiotic 51-I with the respective characteristics of the described antibiotics of the group of aureolic acid suggested that antibiotic 51-I is a new representative of this group.