[Exclusion of immune proteasomes from mouse ascitic carcinoma Krebs-II cells].

Pools of 26S and 20S proteasomes were studied in the spleen, liver, lung, and ascitic carcinoma Krebs-II of mouse. Western blotting demonstrated that the pool of 26S proteasomes in ascitic carcinoma Krebs-II was twice that in control lung cells and did not significantly differ by total 26S proteasome quantities from the spleen and liver. At the same time, the level of immune subunit LMP7 was 12 times lower in it compared to lung proteasomes and 4-5 times lower compared to spleen and liver proteasomes. Immune subunit LMP2 was undetectable by this technique in the ascitic carcinoma in contrast to the lung, spleen, and liver. All immune subunits in the studied organs and ascitic carcinoma Krebs-II are components of 26S but not 20S proteasomes.

[Effects of exogenous poly(A)+ mRNA on antigenic properties and growth of Krebs-2 tumor cells]. / Vliianie ékzogennoi poli(A)+ mRNK na antigennye svoistva i rost kletok opukholi Krebs-2.

The treatment of Krebs-2 ascitic tumor cells (TC) with total RNA from the liver of Wistar rats (2 mg/ml) altered their antigenicity. As a result, the growth of treated TC in contrast with untreated TC was inhibited when transplanted i. m. to mice preimmunized with rat liver homogenate. Investigations of poly(A+)mRNA, rRNA and tRNA isolated from the same tissue established that the alteration of antigenicity is due to mRNA (8-24 micrograms/ml). In the cytotoxicity assay with antisera against rat Wistar antigens, the expression of rat antigens in TC treated mRNA was observed in the next cell generations.

[Appearance of new transplantation antigens in tumor cells treated with RNA]. / Poiavlenie novykh transplantatsionnykh antigenov v opukholevykh kletkakh, obrabotannykh preparatami RNK.

Immunization of mice with the Wistar rat liver tissue increased their resistance to the subsequent intramuscular transplantation of Krebs-2 tumour cells preincubated with the rat liver RNA and did not affect the transplantability and growth of the same untreated tumour cells. The growth of the tumour cells pretreated with allogenic RNA did not differ from the growth of the untreated tumour cells when the mice were immunized with material genotypically different from the RNA tissue-source. When the immunizing tissue and RNA source were genotypically identical, the mass of the tumours growing in three tested mice strains (A/He, CC57BR, BALB/c) was 40-50% less than that of untreated tumours and the enhancement effect was observed in C3Hf mice. It is suggested that RNA preparations induce the appearance of the transplant antigens in tumour cells similar to those of RNA donors tissues. The effect of RNA preparations was abolished by RNAse incubation.

[Effect of a number of antitumor preparations on RNA- and protein-synthesizing processes and viral interferon induction in Krebs 2 ascites carcinoma cells]. / Izuchenie vliianiia riada protivoopukholevykh preparatov na RNK- i beolksinteziruiushchie protsessy i virusnuiu induktsiiu interferona v kletkakh astsitnoi kartsinomy Krebs-II.

Antitumor drugs: adenosine cyclophosphane, adenosine thiophosphamide, colchamine thiophosphamide, and tribetamide inhibited RNA biosynthesis in Krebs-II ascitic carcinoma cells and in similar concentrations they were much less inhibiting for protein-synthesizing processes (in cells and cell-free protein-synthesizing system). The drugs could inhibit interferon synthesis, possibly after virus induction, in Krebs-II ascitic carcinoma cells only in concentrations significantly inhibiting the synthesis of cellular macromolecules.

[High-polymeric xenogenic RNA as an antitumor immunity stimulator]. / Vysokopolimernaia ksenogennaia RNK kak stimuliator protivoopukholevogo immuniteta.

To immunize CC57BR mice a suspension of live cells of Krebs-2 ascites tumour was administered intradermally into the tail partially amputated afterwards. The growth of the tumour transplanted intraperitoneally was inhibited by 23% only after twofold immunization. Single immunization with tumour cell incubated with the cattle liver RNA preparation in conjunction with intraperitoneal administration of RNA following tumour transplantation inhibited its growth by 43--53%, while twofold administration by 84--88%. The high polymeric fraction of the preparation enhanced the immunization effect to the same measures the initial overall preparation. The treatment of the preparation with RNAase and partial depolymerization of RNA in the course of isolation resulted in the activity loss. It is concluded that the capacity of the RNA preparation for stimulating antitumour immunity is due to high polymeric fraction of RNA.

[Differences in the properties of the interferons produced by the leukocytes of healthy persons and of cancer and leukemia patients]. / Razlichiia v svoistvakh interferonov, produtsiruemykh leikotsitami krovi zdorovykh liudei, bol'nykh rakom i leikozom.

In vitro production of interferon by blood leukocytes from patients with lymphosarcoma, lymphogranulomatosis, leukemia, cancer tumours, pneumonia, as well as by leukocytes of mice with Rauscher leukemia, and mice in the condition of hyporeactivity to interferon inducer was studied. Alongside with quantitative differences in interferon production, biological differences in the properties of interferons produced of normal and sick humans and animals were revealed. The biological differences consist in that the interferon produced by leukocytes from cancer and leukemia patients interacting with homologous cell culture is conducive to more rapid formation of resistance to the indicator virus than the interferon produced by normal leukocytes. Thus, resistance of the homologous cell culture to the infection with the indicator vesicular stomatitis virus developed within 1--2 hours after contact with leukocyte interferon from patients and only within 5--6 hours after contact with that of normal subjects. This finding is not specific for cancer and leukemia, as the same was observed with specimens from patients with pneumonia and from mice hyporeactive to interferon inducer. It is suggested that patients with cancer and leukemia have a state of interferon hyporeactivity.

Stimulation of tumor growth in mice by high doses of BCG.

The growth of Krebs-2 carcinoma in BCG-prevaccinated virgin female C57BL/6, CC57BR/M, and C3Hf mice was studied in relation to the number of living mycobacteria in the organism. When the number of mycobacteria was high, tumor growth was stimulated. After the bacteria were eliminated, tumor growth was inhibited. The effect of BCG was based, on the one hand, on the diversion of effector cells, presumably macrophages, responsible for tumor defense and, on the other hand, on the activation of the pool of these cells. The conclusions were reached that high doses of BCG may be dangerous in human cancer immunotherapy and that patients predisposed to neoplastic disease should be revaccinated with BCG.

[Mechanisms of the immunodepression caused by ortho-aminoazotoluene and its noncarcinogenic analog in mice]. / Mekhanizmy immunodepresii, vyzvaemoi u myshei u myshei orto-aminoazotoluolom i ego nekantserogennym analogom.

Single injections of ortho-aminoazotoluene (OAT) or aminoazobenzene (AB) decrease the immune response of DD mice to the strain-nonspecific Krebs-2 tumor. The immunosuppressive action of AB is due to its toxicity for lymphoid cells, whereas the OAT effect is mediated by adrenal glands. After OAT injection,II-oxycorticosteroids level is elevated although their production by adrenal glands is not increased. The accumulation of glucocorticoids in blood after OAT injection is assumed to be the result of a decreased hormone utilization because of the blockade of receptor proteins or metabolizing enzymes in liver cells by a carcinogen.

Inhibition and stimulation of the growth of Krebs-2 carcinoma by BCG vaccine.

The effect of BCG vaccine on the growth of imtransplants of Krebs-2 carcinoma in mice was studied. The simultaneous injection of BCG and tumor cells either inhibited tumor growth (BCG given in admixture with tumor cells) or stimulated it (BCG injected contralateral to the tumor transplantation site). The BCG dose was directly related to the effect. Tumor growth was also stimulated by the ip injection of starch or liquid paraffin. In these experiments, the BCG effect was attributed to the redistribution of cells involved in nonspecific and specific tumor resistance. Shortly after BCG prevaccination, particularly when BCG doses were high and mice were susceptible to vaccine infection, BCG was either without effect or stimulated tumor growth; later, however, tumor growth was inhibited regardless of the BCG dose and the injection site of the BCG. The effect of BCG prevaccination was suggested to be due to: 1)the distraction of macrophages and T-lymphocytes to defend the host against the multiplying mycobacteria, and 2)the activation of the pool of these cells that become capable to participate in antitumor resistance after mycobacteria elimination.

[Stimulation of the inhibiting effect of interferon on the growth of ascitic carcinoma in relation to host responsiveness and cells]. / Stimuliruiushchee ili ingibiruiushchee vliianie interferona na razvitie astsitnoi kartsinomy v zavismosti ot reaktivnosti organizma i kletok

When Krebs-2 ascitic carcinoma is transplanted to mice, administration of interferon may produce either a stimulating or an inhibiting effect on replication of carcinoma cells in the peritoneal cavity depending on the responsiveness of mice (intact or vaccinated with Newcastle disease virus) and the state of the transplanted cells ("common" or "tolerant"). Parallelism was observed in changes of the intensity of cell multiplications and indices of their enzymatic activity under the influence of exogenic interferon.

[Reasons for lowered resistance to Krebs 2 ascitic carcinoma in mice in a state of hyporeactivity (tolerance) to a viral interferon inducer]. / Prichiny snizheniia rezistentnosti k astsitnoi kartsinome Krebs-2 u myshei v sostoianii giporeaktivnosti (tolerantnosti) k virusnomu induktoru interferona

Decreased resistance to Krebs-2 ascitic carcinoma was demonstrated in mice which were in the state of hyporesponsiveness (tolerance) to virus interferon inducer (NDV) and increased resistance of the control mice to transplantation of tolerant carcinoma cells. Manifestations of tolerance in peritoneal and carcinoma cells were shown to be identical: interferon production and reproduction of vesicular stomatitis virus were inhibited, the number of viable cells was reduced, masked infection with NDV was detected, and the activity of cell enzymes was similarly changed. It is assumed that cellular manifestations of tolerance are the cause of reduced resistance of tolerant mice to ascitic carcinoma.

Antimitotic agents and tumor regression.

The selective action of nonantigenic tissue extracts on malignant cells was demonstrated using tissue culture techniques. The mitotic index of three strains of neoplastic cells was significantly reduced by the use of extracts which previously had proven effective in adversely affecting the development of spontaneous neoplasms. Under the same conditions the division rate of normal cells in tissue culture was not affected by the extracts. The malignant cells used were the Krebs 2, Sarcoma 180 and the L1210 leukemia. The normal cells were the L929 fibroblasts and epithelial-like cells from bone marrow and corneal tissue.