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The response of human and animal cells to the action of fusicoccin (FC), a fungal metabolite with phytohormonal properties, was evaluated. The capacity of FC for inducing the synthesis of early interferon (IFN), supplied into the blood serum of common white mice, and for enhancing the natural cytotoxic activity of human lymphocytes in vitro was established. The metabolism of actively proliferating monocytic leukemia cells J-96 and human ovarian carcinoma cells CaOv, as well as mouse fibroblasts L-929, was found to be inhibited under the in vitro action of FC. The common character of the mechanisms of action of FC and IFN having antiproliferative and immunomodulating activity is discussed.

Nitric oxide (NO) acts as a short-lived paracrine factor and selectively activates transcription of certain genes. The spectrum of inducible genes was studied in primary chondrocytes. A cDNA library was obtained by subtraction hybridization with RNAs isolated from rabbit chondrocytes before and after treatment with nitrosoglutathione, an NO-generating agent. Some of the cloned cDNAs were homologous to known mammalian genes and human EST. NO-dependent transcriptional activation was demonstrated for the stromelysin 1 and cyclooxygenase 2 genes and, for the first time, for mcl1 coding for an apoptosis suppressor.

Relationship between the priming effects of interferon (IFN)-alpha and -gamma and the standard IFN production by peripheral blood leukocytes was evaluated in 25 volunteers (13 men and 12 women, mean age 35.3 years). Priming of IFN-alpha and IFN-gamma production positively correlated with the standard IFN-alpha and IFN-gamma synthesis, respectively. On the other hand, primed production of IFN-alpha negatively correlated with that of IFN-gamma. Possible role of types I and II IFN interactions in the maintenance of physiological regulatory balance is discussed.

A comparative study of surface membranes of human cell J-96 and J-48 cultures with different sensitivity to alpha/beta interferon (IF). Reduced sensitivity of J-41 cells to IF-alpha/beta was found to be accompanied by a loss of highly specific receptors for IF-alpha, the lack of changes in the cell surface structures upon treatment with IF-alpha/beta, reduced intensity of cell fusion upon successive treatment with IF and polyethylene glycol. The results are discussed in connection with the observed changes in the activity of superoxide dismutase in J-96 and J-41 cell lines after treatment with IF.

The effect of human leukocyte interferon (HLI) on three human cell cultures of different origin was studied. HLI inhibited the mitotic activity (MA) of human ovary carcinoma cell culture and to a lower extent that of a diploid cell culture. At the same time HLI preparation exerted a nonspecific stimulating effect on MA of the primary human embryo cell culture. The optimal conditions for the determination of the antimitotic effect of interferon on cells of tumor origin include: a seed dose of 5 X 10(4) cells/ml, addition of interferon to the culture 24 hours after cell seeding; the maximum effect of interferon is observed at 24 hours after addition to the culture.

Heterochromatin of chromosomes is studied by means of a C-banding technique for the J-96 line of human cells, which is susceptible to enteroviruses and for the J-41 cell line derived from this culture and possessing high specific resistance to Coxsackie B viruses. The data obtained demonstrate stability of variform C-heterochromatin of chromosome pairs 1, 9 16 and certain marker chromosomes in the course of long-term cultivation.

The role of chromosomes 2, 5, 16, and 21 in production and effect of human interferon was checked in human diploid cells, human heteroploid cells J-96 and clone J-41 thereof. The J-41 cells were found to have a lower number of chromosomes 2 as compared to the other cells under study; J-41 cells produce less interferon than the other cells. Most J-41 cells lack chromosome 21. Unlike the other two cell cultures, these cells do not produce antivirus state after treatment with interferon. The number of chromosomes 16 is larger in J-96 cells than in diploid ones, and they are less sensitive to interferon than diploid cells. The experimental results confirm the importance of chromosome 2 for coding for interferon production, other chromosomes taking part in the regulation of this process. The gene of sensitivity to interferon is localized in chromosome 21, the regulator gene coding the production of repressor of sensitivity to interferon is in chromosome 16.

The application of NORs and R-bands for simultaneous staining of nucleolar organizer regions and banding chromosomes of stable human line is proposed. This technique was applied to studies on the human stable cell line J-96.

The study was done on a subline of cells reverting to sensitivity to Coxsackie B3 virus after treatment of J-41 cells resistant to this virus with a homogenate prepared from the sensitive J-96 cell culture. Cytogenetic examinations of this cell subline showed its karyological characteristics to approach those of the sensitive J-96 culture. The modal number of chromosomes and the number of chromosomes 2, 9, 11, 12, and 21 were completely restored and marker chromosomes typical of the sensitive culture appeared. In the reverted subline there was almost no marker chromosomes peculiar for the resistant J-41 culture. In addition, a decrease in the number of chromosomes 1 and 19 replicas as compared with J-96 and J-41 culture cells and the presence of marker chromosomes not found in the original cultures indicate that this subline has its own distinctive characteristics.

The antiproliferative (AP) action of human leukocytic interferon (HLI) of varying degrees of purification was studied and compared in cultures of human cells differing in interferon sensitivity. The concentrated and purified preparations of HLI suppressed the incorporation of 3H-thymidine and mitotic activities of the cultures sensitive to HLI of the cells, affecting, but insignificantly, the proliferation of the resistant cell culture. Poorly purified HLI suppressed the proliferation of both cell types. This indicates that native HLI contains impurities that have an AP action and exerts no antiviral activity.

The cell fusion has been studied in human reticular cell cultures J-96 and J-41 treated with the Sendai virus or with polyethylene glycol 1000 and 6000. The J-96 cells have a high alkaline phosphatase activity, in J-41 cells the enzyme is not detectable. No heterogenous alkaline phosphatase activity was seen in the protoplasm of symplasts 18 hours after virus cell fusion. It has been shown with polyethylene glycol treatment that during the fusion of cells J-96 and J-41 the enzyme activity was spreading over the symplast protoplasm.

Induction of 2'-5'-oligoadenylatesynthetase (2-5A synthetase) by interferons and theophylline by means of activation of cAMP-system in interferon susceptible and resistant cell lines were studied. In interferon resistant cell lines the basal activity of 2-5A synthetase exceeded the level of the same enzyme in interferon susceptible cell lines. Activity of 2-5A synthetase is increased in interferon susceptible cell lines by interferon treatment, but the activity of the enzyme is not altered in interferon resistant cell lines. Among the studied cell lines the induction of 2-5A synthetase by theophylline was possible only in L929 cell line. The common mechanism for the absence of 2-5A synthetase induction by interferon and theophylline in interferon resistant cells is discussed.

A continuous cell line of human spleen has been obtained. The methods of seeding large numbers of cells and prolonged cultivation of the culture played an important role in isolation of this cell line; both methods have contributed to the creation of conditions for gradual reconstruction of the cellular metabolism in the absence of which the cells wound not be able to get adapted to contiuous cultivation. As the authors failed to obtain a contiuous cell line from a single cell colony the method of "shaking" was applied. The culture was obtained only in case of a 1% PHA solution was added to the nutrient medium.

When the Drosophila cells were infected with the mixo- and arboviruses, in case of influenza A/WSN virus a rise in the titre and slight cytopathogenic effect with the subsequent decrease in the titre was observed. Since the decrease in the virus titer was not observed when actinomycin D was added, it was supposed that interferonlike inhibitor may be produced by the infected cells. Vacuolization and increase in the size of the infected cells were caused by all the nuclear polyhedrosis viruses tested. The number of the infected cells depended on the virus type and multiplicity of the infection.

The paper is concerned with comparative cytogenetic studies of human cell line J-96 and subline J-41 derived from it. Application of G-, R- and C-techniques for differential staining of chromosomes made it possible to determine both numeric and structural changes in chromosomes of the resistant subline as compared to the initial one. The mechanisms contributing to a decrease in the normal chromosome number and to appearance of new marker chromosomes in the resistant subline cells are discussed as well as the possible relation of the found chromosome changes to the loss of cell sensitivity to the Coxsackie B3 virus.