[The role of prostaglandins type E in tumor cells during their contact with NK-cells in vitro]. / Rol' prostaglandinov tipa E v opukholevykh kletkakh pri ikh kontakte s NK-kletkami in vitro.

Active PGE--secretion by malignant tumour cells of Syrian hamsters was demonstrated 30 min after their contact with NK-cells in vitro. The duration of PGE--secretion depended upon the ratio of tumour cells and NK--cells, engaged in contact. Increase of the number of NK--cells (bound to tumour cells) up to 10:1-20:1 led to rapid release of PGE from majority of tumour cells; in this case PGE release was continued not longer than 1.5-2.0 hours. The active release of PGE can be stopped after the contact of tumour and NK--cells by indomethacin at any moment of its secretion.

[Secretion of prostaglandin E by cells of human thymoma MOLT-4 and their sensitivity to cytotoxic action of NK-cells]. / Sekretsiia prostaglandina E kletkami timomy cheloveka MOLT-4 i ikh chuvstvitel'nost' k tsitotoksicheskomu deistviiu NK-kletok.

It was demonstrated that thymoma cells of MOLT-4 strain which are the standard cell targets of cytotoxic tests (CT) with NK-cells are rapidly releasing PGE in contact with NK-cells; as a consequence the depression of cytotoxic activity (CTA) of NK-cells takes place. The significant decrease of CTA of NK-cells was observed when the absolute number of MOLT-4 target cells participating in CT increased. Correspondingly the susceptibility of MOLT-4 cells as a target in CT is decreased. The levels of susceptibility of MOLT-4 cells to NK-cell cytotoxicity and CTA of NK-cells retained, or even increased, after the pretreatment of MOLT-4 cells with indomethacin.

[The secretion of type-E prostaglandins and the sensitivity to hydrogen peroxide of Syrian hamster clone cells transformed by the Rous sarcoma virus]. / Sekretsiia prostaglandinov tipa E i chuvstvitel'nost' k perekisi vodoroda klonov kletok siriiskogo khomiachka, transformirovannykh virusom sarkomy Rausa.

Seven clonal sublines of the strain of syrian hamster embryo cells transformed in vitro by the Rous sarcoma virus were obtained. All clones possessed both high resistance to damage by hydrogen peroxide and a capacity to release E-type prostaglandins in response to contact with NK-cells in vitro. The clones did not differ from each other and from the parent population in respect to these qualitative properties. Possible relation between these two properties and their role in resistance of transformed cells to cytotoxic activity of macrophages, neutrophils and NK-cells and thus to their ability to survive in vivo are discussed.

[Enzyme activity of adenosine metabolism in human natural killers (NK cells) during the activation and suppression of their cytotoxic activity]. / Aktivnost' fermentov obmena adenozina v estestvennykh killerakh (NK-kletkakh) cheloveka v usloviiakh aktivatsii i podavleniia ikh tsitotoksicheskoi aktivnosti.

Experiments in vitro were made to study adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity in NK after their treatment with interferon inductor--Newcastle disease virus (NDV) or with prostaglandin E2 (PGE2). It has been established that treatment of human NK with NDV leads to increasing of their cytotoxic activity (CTA), which is accompanied by rising of ADA activity and reducing of 5-N activity in these cells. Decrease of CTA under the influence of PGE2 occurs together with reduction of ADA activity and increase of 5-N activity in human NK. Changes in NK activity under the influence of various exogenous or endogenous factors may be due to the modification of activity of adenosine metabolism enzymes in these cells.

[Effect of the prostaglandin E produced by tumor cells on the enzymatic activity of adenosine metabolism and on human natural killer cytotoxic activity]. / Vliianie produtsiruemogo opukholevymi kletkami prostaglandina E na aktivnost' fermentov obmena adenozina i tsitotoksicheskuiu aktivnost' estestvennykh killernykh kletok cheloveka.

Adenosine deaminase (ADA) and 5'-nucleotidase (5'-N) activity and cytotoxic activity (CTA) of natural killer cells (NK-cells) isolated from human peripheral blood were studied. These cells were affected by culture medium obtained after the contact of tumour cells with NK-cells, the degree of malignancy in these cells being different. It has been established that pretreatment of NK-cells with culture medium from highly malignant cells and containing PGE, causes a sharp inhibition of their CTA, which is accompanied by an essential decrease of the ADA activity and an increase of the 5'-N activity in these cells as compared with the control.

[Secretion of type-E prostaglandin by tumor cells of different degrees of malignancy when in contact with effectors of natural resistance]. / Sekretsiia prostaglandina tipa E opukholevymi kletkami raznoi stepeni zlokachestvennosti pri ikh kontakte s éffektorami estestvennoi rezistentnosti.

It was demonstrated that short-term contact of highly malignant tumour cells with NK-cells, neutrophils and macrophages induced rapid PGE secretion into the culture medium. PGE is detected in the culture fluids by the biological test based on inhibition of cytotoxic activity of NK-cells in standard cytotoxic tests. In the direct radioimmunoassay no PGE release was detected when low malignant tumour cells contact with effector cells of natural resistance system as well as after malignant tumour cell pretreatment with indomethacin. There was no increase in PGE secretion by the malignant tumour cells after their in vitro contact with red cells, normal hamster embryo cells and tumour cells of different origin.

[Secretion of prostaglandin type E (PGE) by tumor cells of Syrian hamsters in in vitro contact with natural killers]. / Sekretsiia prostaglandinov tipa E (PGE) opukholevymi kletkami siriiskogo khomiaka pri ikh kontakte in vitro s estestvennymi killerami.

The ability of Syrian hamster tumor cells of the same origin but with different degrees of malignancy to secrete prostaglandin E (PGE) was studied following their in vitro contact with Syrian hamster natural killer cells (NK cells). Syrian hamster NK cells were shown to lose significantly cytotoxic activity after their contact with malignant tumor cells. Short-term in vitro contact of malignant tumor cells with human and Syrian hamster NK cells resulted in a rapid PGE secretion into the culturing medium. PGE was determined in the culturing medium, using the biological test, described in the paper, or direct radioimmunoassay. No PGE secretion was observed after the treatment of tumor cells with indomethacin. It is assumed that PGE secretion by malignant tumor cells is one of the mechanisms of their protection against natural killer cells.

[Inhibition of the cytotoxic activity of natural killer cells by glycosphingolipids. Effect of the structure of carbohydrate chains]. / Ingibirovanie tsitotoksicheskoi aktivnosti estestvennykh killerov glikosfingolipidami. Vliianie struktury oligosakharidnykh tsepei.

The ability of various glycosphingolipids to inhibit the cytotoxic activity of natural killer (NK) cells was studied. The inhibitory effect was found to depend on the structure and concentration of the glycosphingolipids. Gangliosides SiaLacCer inhibited the NK activity most effectively and their inhibitory effect depended on the structure of sialic acids: the N-acetyl form was more active than the N-glycoloyl form. Elongation of the carbohydrate chain decreased the inhibitory effect and monosialogangliosides NeuGcGgOse3Cer and NeuAcGgOse4Cer were practically inactive. The inhibitory ability of disialogangliosides depended on the structure of the carbohydrate chain as well as on the structure and attachment site of the sialic acids. Previously it was found that ganglioside (NeuAc)2LacCer, which is absent or very low in normal blood, is produced by a number of tumors and alongside with NeuAcLacCer is present in elevated amounts in the blood of tumor-bearing subjects. Elevated concentration of these gangliosides in the blood of tumor hosts may inhibit apparently the NK activity and thus contribute to the escape of tumor cells from host immune surveillance.

[Cytotoxic activity and activation ability of Syrian hamster NK cells isolated in the Percoll density gradient]. / Tsitotoksicheskaia aktivnost' i sposobnost' k aktivatsii vydelennykh v gradiente plotnosti perkolla EK-kletok siriiskogo khomiaka.

Natural killer cells possessing cytotoxic activity (CTA) and the ability to be activated by an interferon inductor and Newcastle disease virus, were isolated from blood, spleen and bone marrow of Syrian hamsters in the discontinuous Percoll density gradient. According to morphological criteria these cells were identified as large granular lymphocytes (LGL). The largest amount of LGL was isolated in the fraction containing 52-55% Percoll. CTA of cells from this fraction was the highest as compared to nonfractionated control or cells from other Percoll fractions. Effective (3-fold) activation of bone marrow cells isolated in the fraction of 49% Percoll with initially low CTA suggests that this Percoll fraction contains noncytotoxic precursors of NK cells.

[Isolation and identification of normal killers from Syrian hamsters]. / Vydelenie i identifikatsiia normal'nykh killerov siriiskikh khomiakov.

Natural killers (NK cells) possessing cytotoxic activity were isolated from the blood, spleen and bone marrow of Syrian hamsters in discontinuous Percoll density gradient. These cells were morphologically identified as granular lymphocytes (GL). The largest amount of GL was isolated from the fraction containing 52-55% of Percoll. Cytotoxic activity of cells in this fraction was the highest, as compared to nonfractionated control or cells in other Percoll fractions.

[Characteristics of the NK cells in Syrian hamsters carrying tumors with varying metastatic and resistance-suppressing activity]. / Kharakteristika NK-kletok u siriiskikh khomiakov-nositelei opukholei s razlichnoi metastaticheskoi i rezistentnost' podavliaiushchei aktivnost'iu.

Experiments in vivo and in vitro were made to study the effects of HETR-MLN-8 and HETR tumor cells differing in metastatic ability and inhibition of the natural host resistance to tumor on cytotoxic activity of NK from Syrian hamsters. Marked inhibition of cytotoxicity and ability for interferon activation was detected in NK isolated from tumors (as compared with blood), with that inhibition being far more pronounced in highly malignant HETR-MLN-8 tumors. This may indicate a direct inhibitory action of the tumor or its products on NK cytotoxicity. The in-vitro competition inhibition test yielded results showing that HETR-MLN-8 cells capable of in-vivo inhibition of the natural host resistance to the tumor also display much more demonstrable ability for in-vitro inhibition of NK cytotoxicity as compared to HETR cells.

[Characteristics of natural killer cells (NK cells) and features of the cytotoxic test in Syrian hamsters]. / Kharakteristika normal'nykh killerov (NK-kletok) i osobennosti tsitotoksicheskogo testa u siriiskikh khomiakov.

The cytotoxic test in vitro with the use of xenogeneic target cells of human myeloma, strain K-562, labeled with 51Cr has demonstrated natural cytotoxicity of lymphoid cells from noninbred Syrian hamsters. This cytotoxicity occurs at the cost of non-adherent splenocytes. NK may be isolated over the gradient density of ficoll (1.078), selective for large granular lymphocytes. To detect the maximal lytic activity of NK from Syrian hamsters in the cytotoxic test in vitro, they should be brought into 10-12 hour contact with sensitive target cells K-562. In Syrian hamsters, the highest natural cytotoxicity is shown by the cells of the blood and spleen. In the bone marrow and thymus, it is little pronounced and is virtually absent from the peripheral lymph nodes.

[Activation of natural killers (NK cells) in normal Syrian hamsters and tumor-bearing hamsters by the Newcastle disease virus]. / Aktivatsiia normal'nykh killerov (NK-kletok) normal'nykh siriiskikh khomiakov i khomiakov-nositelei opukholei virusom bolezni N'iukasla.

Natural cytotoxicity of non-adherent lymphoid spleen cells from random-bred Syrian hamsters was demonstrated in the cytotoxic test in vitro with the use of xenogeneic human myeloma target cells (strain K-562) labeled with 51Cr. Cytotoxic natural killers (NK) could be isolated in the Ficoll gradient of 1.078 density, selective for large granular lymphocytes. The maximal lytic activity of NK was observed in the cytotoxic test in vitro after 10-12-hour contact with sensitive K-562 target cells. The highest NK activity was observed in blood and spleen cells. In bone marrow and thymic cells, it was less potent. NK activity was almost absent from peripheral lymph nodes.

[Effect of bone marrow, spleen, and peritoneal exudate cells on metastasis of tumor cells into the lungs of Syrian hamsters]. / Vliianie kletok kostnogo mozga, selezenki i peritoneal'nogo ékssudata na metastazirovanie opukholevykh kletok v legkikh siriiskikh khomiakov.

Nonactivated cells of the bone marrow (BM), spleen (SC) and peritoneal exudate (PE) of normal randombred Syrian hamsters are capable to inhibit (when administered to the blood channel) spontaneous metastases and colony-formation of tumor cells in the lungs of Syrian hamsters. The inhibitory effect was recorded after administering cells of the normal BM and PE but not of SC. The inhibitory effect on pulmonary metastases was in good agreement with the dose of effector cells. Inhibition of pulmonary metastases was effected by a single administration of BM and PE cells 5-8 days before inoculation of tumor cells, in conjunction with these cells and even within the first 5 days after administering tumor cells to the blood flow. In 50-60% of the animals, pulmonary metastases were completely suppressed; in the remainder of the animals, the rate of metastases was either decreased or the pattern of pulmonary metastases occurrence was similar to that seen in the control.

[Resistance-suppressing activity of transformed Syrian hamster cells and their ability to metastasize]. / Podavliaiushchaia rezistentnost' aktivnost' transformirovannykh kletok siriiskogo khomiaka i ikh sposobnost' k metastazirovaniiu.

Hamster embryo cells spontaneously transformed in vitro (HETr) with low metastatic activity were not capable to depress natural antitumor resistance in vivo in contrast to some other lines of Syrian hamster tumor cells. The resistance, depressing and metastatic activities of HETr parental cells and their variants obtained from lung metastases were studied and compared. The direct correlation was found between the resistance-depressing and metastatic activities of the cell variants studied. Five of eight cell variants obtained from lung metastases ocf HETr were capable to depress natural host resistance to the growth of transplanted tumor cells. They were the most active variants in the lung colonization test. It is suggested that in the course of metastasizing there takes place the selection of the tumor cell variants capable of depressing natural antitumor host resistance.

[Quantitative analysis of the immunogenic activity of SV40 virus and the cells of tumors induced by this virus]. / Kolichestvennyi analiz immunogennoi aktivnosti virusa SV40 i kletok opukholi, indutsirovannoi étim virusom.

The study of specific antitumour immunity induced by onogenic SV40 virus and by cell of SV40 virus and by cells of SV40-induced tumour of Syrian hamster demonstrated direct correlation between the level of specific antitumour resistance and the immunizing virus and tumour cell doses. The minimal resistance-inducing dose of the wild type SV40 virus strain was 10 times higher than that of ts A-30 mutant of this virus. Minimal resistance-inducing dose of irradiated cells of the tumour was about 9 x 10(5) cells; a 10-fold increase of this dose significantly increased the specific antitumour immunity level.

[Comparative immunogenicity of irradiated and nonirradiated syngeneic and xenogeneic tumor cells containing a common specific transplantation antigen]. / Sravnitel'naia immunogennost' obluchennykh i neobluchennykh singennykh i ksenogennykh opukholevykh kletok, soderzhashchikh obshchii spetsificheskii transplantatsionnyi antigen.

The authors compared the immunogenic activity for Syrian hamsters of native and irradiated syngeneic and xenogeneic tumour cells bearing on their surface common and SV40-specific transplantational antigen. The results obtained showed syngeneic tumour cells to be more immunogenic for the recipient than the xenogeneic tumour cells containing an antigen of the same specificity. Irradiation renders tumour cells, including the xenogeneic ones, more immunogenic, this possibly being associated with the capacity of nonirradiated cells to escape from immune recognition through their ability to divide.

[Thermal sensitivity of specific transplantation antigens of the tumor-cell membrane]. / Termochuvstvitel'nost' spetsificheskikh transplantatsionnykh antigenov kletochnoi membrany opukholevykh kletok.

Study of temperature-sensitivity of the tumour specific transplantation antigen (TSTA) on the cell membrane of SV40-induced tumours and spontaneous hepatoma of inbred Syrian hamsters, as well as in the monkey cells infected in vitro with SV40 virus (ts-mutant) demonstrated high thermolability of TSTA. Heating such cells at 56 degrees C for 30-60 min led to complete loss of their immunogenic activity. Moreover, in the animals immunized with heated tumour cells the test-tumour cell growth was regularly enhanced.