[Isolation of sarcoma virus from noninbred rats]. / Vydelenie virusa sarkomy ot besporodnykh krys.

The data are presented on the activation of endogenous retrovirus in vaccinia virus--malignant transformed cells of rat tissue culture. Infection of the cells by Mazurenko mouse leukemia virus induced rat sarcoma virus. The latter was formed as a result of recombination of sarcoma virus-specific sequences received from the rat cells malignantly transformed by vaccinia virus and virus-helper (Mazurenko mouse leukemia virus).

[Effect of a mixed viral infection on the development of neoplasms induced by oncogenic viruses]. / Vliianie smeshannoi virusnoi infektsii na razvitie neoplazii, indutsirovannykh onkogennymi virusami.

Data are presented concerning the stimulating effect of vaccinia and herpes simplex type 2 viruses on the development of leukemia in BALB/C, C57BL/6, and AKR mice. Mixed infection with PAB-49 and Marek disease virus of brown leghorn chickens was shown to increase the frequency of lymphomas development.

[Proto-oncogene expression in mouse leukemia induced by the Mazurenko virus]. / Ekspressiia protoonkogenov pri leikoze myshei, vyzvannom virusom Mazurenko.

The expression of 8 protooncogenes was examined in different types of murine leukemia induced by Mazurenko virus. C-myc-specific RNA (2, 3 kb and 1.8 kb) was revealed only in tissues of mice with thymomas (T-cell leukemias) but not with generalized leukemias. 1.4 kb Ha-ras RNA transcripts were observed in all RNA species from leukemic mice. The highest expression of the above oncogenes was noted in thymus and lymph nodes, in spleen and liver the expression was lower. Ki-ras, abl, fos, myb, erb and B-lym-specific RNA expression was not observed in any of the tissues tested. The expression of C-myc RNA is believed to be the result of C-myc activation due to provirus integration.

[Possible connection of the vaccinia virus and carcinogenesis]. / O vozmozhnoi sviazi virusa ospovaktsiny s kantserogenezom.

The data are presented indicating a possible carcinogenic danger of vaccinia virus. Vaccinia virus with reduced lytic properties was shown to be capable of inducing morphological and malignant transformation of cells of primary mammal tissue cultures (mouse, rat, man).

[Effect of vaccination of mice with endogenous retrovirus on the development of tumors induced by gamma-irradiation or 7,12-dimethylbenz[a]anthracene]. / Vliianie vaktsinatsii myshei éndogennym retrovirusom na razvitie opukholei, indutsirovannykh gamma-oblucheniem ili 7,12-dimetilbenz[a]antratsenom.

Mouse vaccination with alive endogenous N-tropic virus OA-3 inhibited and decreased the development of the Rauscher leukemia in C57B1/6 mice (B-type) and SWR mice (N-type) as well as the development 7,12-dimethyl benzanthracene (DMBA)-induced tumours in mouse hybrids (neither N-, nor B-types). The effect of vaccination was DMBA- or MLV-P-dose-dependent. Vaccination with the same virus did not affect the incidence of gamma-irradiation-induced leukemia in CBA mice (N-type) and C57B1/6 mice while it increased twice the incidence of radiation leukemia in DBA mice (N-type). However, the incidence of thymomas lowered in radiation leukemia-bearing vaccinated mice of all the 3 strains, which may result from inhibition of murine thymotropic endogenous virus reproduction. The data obtained indicate the participation of murine own endogenous viruses in DMBA- or gamma-irradiation induced carcinogenesis.

[Malignant cell transformation in rats in vitro as affected by the variolovaccine virus]. / Zlokachestvennaia transformatsiia kletok krys in vitro pod vliianiem virusa ospovaktsiny.

The capacity of the variolovaccine virus with low cytopathogenic activity to cause morphologic and malignant transformation of normal rat cells in vitro is detected. The transformed cells induced tumours in gamma-irradiated rats.

[Long-term cultivation of the Mazurenko leukemia virus in mouse and rat cell lines]. / Dlitel'noe kul'tivirovanie virusa leikoza Mazurenko v kletochnykh liniiakh myshei i krys.

Reproduction of the Mazurenko leukemia virus was studied in cell lines of different origin. Mongrel rat fibroblasts nonproductively transformed with variola vaccine virus proved to be the most adequate system for the virus replication. The leukemogenic virus reproduction in transformed rat cells was observed for 250 days.

Generation of new transforming viruses from SIRC cells "phenotypically transformed" in the medium with low concentrations of serum or calcium ions.

The work reported here demonstrates the possibility of rapid generation of highly transforming viruses from rabbit epithelial corneal cells (SIRC) originated from simian sarcoma associated virus (SSAV). The results of the experiments indicate a possible association of the phenomenon of "phenotypic transformation" with the expression of cellular genes with a potential transforming activity. SIRC/SSAV phenotypic transformation was induced by cultivation of these cells in the medium with a low concentration of serum or calcium ions. During subsequent infection of mink lung fibroblasts the authors succeeded in obtaining two new transforming SSAV isolates which induced transformation foci of various morphological types in cellular lines permissive for SSAV replication.

The development of joint scientific cooperation within the framework of CMEA on the problem of "viral carcinogenesis".

Major trends of research carried by Council for Mutual Economic Assistance (CMEA) member countries in the field of "viral carcinogenesis" of the complex problem "malignant neoplasia" are outlined for the past 10 years. Steady extension and elaboration of the types of cooperation is emphasized. Scientific cooperation of CMEA member countries has been carried out since 1974 under the sponsorship of the Cancer Research Institute, Slovak Academy of Sciences (Czechoslovakia) within the framework of CMEA. Leading oncological institutions of Bulgaria, GDR, Hungary, Poland, USSR and Czechoslovakia have been contributing to the research.

[Vaccinating properties of the Kekava 55 strain of attenuated Marek's disease virus]. / Vaktsiniruiushchie svoistva attenuirovannogo virusa bolezni Mareka, shtamm Kekava 55.

Two attenuated strains of oncogenic herpes virus, Marek's disease virus, were obtained: one by cultivation in chick fibroblast cultures at 37 degrees C, the other at 41 degrees C, i. e. at chicken body temperature. Both attenuated strains throughout a large number of passages retain high vaccination efficacy, on the average 76% and 77.3%, respectively. The virus attenuated at 41 degrees C is superior to that attenuated at 37 degrees C in higher reproduction rate in vitro and, possibly, in a greater range of passages during which good vaccinating properties are retained. Unlike turkey herpes virus, both attenuated strains reduce the spread of the infection markedly.

[Isolation of new transforming viruses from "phenotypically transformed" Sirc cells in a medium with a low concentration of serum or calcium ions]. / Poluchenie novykh transformiruiushchikh virusov iz kletok Sirc, "fentotipicheski transformirovannykh" v srede s nizkoi kontsentratsiei syvorotki ili ionov kal'tsiia.

Possibility of rapid generation of highly transforming viruses from rabbit epithelial corneal cells (Sirc) on the basis of SSAV virus is discussed. The results of the study suggested a relationship between the phenomenon of "phenotypic transformation" with expression of cellular genes and a potential transforming activity. Sirc/SSAV phenotypic transformation was induced by cultivating of cells in a medium with low levels of serum or calcium ions. Subsequent infection of mink lung fibroblasts resulted in generation of 2 new transforming SSAV isolates which induced transformation in cellular lines permissive for SSAV replication. The foci of transformation were of various morphological patterns.

[What the viral theory of tumor origin has contributed to oncology]. / Chto dala onkologii virusnaia teoriia proiskhozhdeniia opukholei.

The viral theory of tumor origin has proved to be an important factor of accumulation of fresh evidence and working out new methods and approaches. The paper contains a summary of this evidence and discusses the problem of the indirect co-carcinogenic effect of tumor-inducing agents. Sometimes it is due to their activation of specific oncogenic viruses. In other cases, as the author suggests, it may be caused by the activation of potential oncogenes (protooncogenes) or normal cells. There are viral and non-viral tumors and human tumors are apparently chiefly non-viral. The author suggests that it is an endogenous disease (protooncogenes and their endogenous activators). The author considers his hypothesis (1962) on the cellular origin of oncogenes and the similarity of their transmission by viruses to microorganism transduction. A similar suggestion was made by P. Vogt and A. D. Altstein ten years later and it has been supported by some findings ever since. The viral theory cannot be regarded as the sole fundamental theory of carcinogenesis.

Attempts ot activate endogenous virus expression with Marek's disease virus DNA.

Several DNAs derived from Marek's disease virus-infected cells and tissues were tested for in vitro infectivity and for the ability to activate avian endogenous type C virus. The DNA isolated from tumour tissue, peripheral blood buffy coat cells, MDV-infected tissue cultures, lymphoblastoid cell lines and feather follicle epithelium cells from MDV-infected birds elicited a negative response in transfection assays. The MDV DNAs isolated did not activate the endogenous type C virus from cell cultures derived from the C, I and M chicken lines. Activation was observed only in one experiment in the early period after transfection with MDV DNA. The treatment with DNase destroyed this MDV DNA activity, and lambda phage DNA and cell DNAs did not activate the endogenous viruses. Repeated experiments failed to confirm the early activation of endogenous viruses.

In vitro studies of a co-carcinogenic effect of vaccinia and herpes group viruses.

The results of studies of a co-carcinogenic effect of two human infectious viruses in tissue culture are reported here. Viable vaccinia virus actively replicating in the cells of primary BALB/c tissue culture and in a number of continuous murine cell lines has been shown to induce in them expression of major structural p30 protein of murine retroviruses. Vaccinia virus has been also shown to cause biochemical transformation of murine cells. Evidence for the capacity of herpes simplex virus type 2 to induce malignant transformation of BALB/3T3 murine cell line has been obtained and confirmed by transplantation to mice. Transformed cell clones did not contain complete infectious herpes simplex virus but were resistant to superinfection with this virus. N-tropic endogenous murine retrovirus of C type with buoyant density in the saccharose density gradient of 1.18 g/cm3 and a reverse transcriptase activity was expressed in the transformed cells. In the virion structure six proteins typical of these viruses with the prevalence of p30 have been demonstrated. Competitive radioimmunoassay revealed a very high level of virus production: p30 level reached 7500 ng p30 R-MuLV per mg of viral protein. Specificity of this results was shown in control experiments.

Virus-viral co-cancerogenesis and the other viral interactions.

The article presents the data obtained by the authors in studies of virus-viral co-cancerogenesis, the interaction between some non-oncogenic viruses and well-known oncogenic viruses, the results of co-cancerogenic effect Marek's disease herpesvirus with the avian leukemia virus and the possibility of phenotype mixing between oncornaviruses belonging to different species in nature.

Increased susceptibility of leukemia-infected chickens to Marek's disease.

Intramuscular (i.m.) injection of RAV-49 into 1--3 day-old chickens infected with Marek's disease herpes virus (MDHV) by contact led to exceedingly high rate of Marek's disease (MD) incidence. According to the data obtained in three experiments 52 out of 108 (48.1%) chickens fell ill in this group. While in the group uninfected with RAV-49 but contactly infected with MDV-Kekava there were only 11 out of 102, (10.7%) incidences. Simultaneous inoculations of RAV-49 and MDV had no effect on MD morbidity. Increased susceptibility of i.m. RAV-49-infected and contactly MDV-infected chickens to MD was abolished by simultaneous inoculation of RAV-49 and herpes virus of turkeys (HVT).