Rat embryonal fibroblasts of the second passage have been immortalized or transformed with the E1A region of the human adenovirus type 5 and the cloned c-Ha-ras oncogene. Several cell lines obtained greatly differ according to the criteria of the transformed phenotype: saturation cell density, the ability to be cloned on a substrate and in soft agar, the ability to give tumors in nude mice. We have transiently transfected these immortalized and transformed cell lines with CAT-plasmids containing the CAT gene under the control of promoters of the "cell-cycle dependent" genes (human hsp70 and protooncogene c-fos). The results showed that the expression of hsp-CAT and fos-CAT plasmids differed in great extent depending on whether the cells were immortalized (E1Aad5) or transformed (E1Aad5+Ha-ras). The role of cellular genes and cellular transcription factors influencing the expression of transiently transfected CAT-plasmids has been discussed.

Problems of the origin, structure and functions, in the cells and tissues, of the so-called proto-oncogenes (c-onc)--cell genes, homologues and oncogene foreparents (v-onc)--are considered in the review. Up-to-date data are given to show the participation of the main groups of proto-oncogenes in the processes of cell division, proliferation and differentiation. The role of c-onc genes is found to be important for fundamental manifestations of the cell life activity. Special attention is paid to the problem of interrelation of the proto-oncogenes with growth factors and their receptors.

In patients with B-cellular chronic lympholeukemia the blood lymphocyte rosette formation with sheep and mouse red cells (SRC and MRS) and estimation of the ratio between SRC- and MRC-receptor carrying lymphocyte subpopulations helps assess the intactness of T-cellular function, disease phase (remission or exacerbation) and prognosis, and patient's sensitivity to chemotherapy.

Four monoclonal antibodies (Mabs) of series IGR-1 and IGR-2 to nuclear antigens of neutrophilic granulocytes of human peripheral blood were obtained. Mabs IGR-1 2B8 and IGR-1 6B5 are bound to their specific antigens in the nuclei of all the investigated human cell lines. These Mabs were also specific for metaphase chromosomes of cell lines HL-60 and U-937. Investigations on the ultrastructural level showed that Mabs IGR-1 6B5 reacted with the HL-60 nuclear heterochromatin region. Mabs IGR-1 3D3 and IGR-2 2F1 manifested high specificity only for the nuclei of mature neutrophils and of plasma cells.

The authors have presented the current data on so-called Ph'-negative chronic myeloleukemia (CML). A detailed clinico-hematologic analysis has proved that most of patients with unchanged chromosome 22 have other myeloproliferative disease, most often it is chronic myelomonocytic leukemia. In some CML patients Ph'-chromosome is masked as a result of translocations, in other patients, although chromosome 22 is unchanged, the molecular-genetic marker of CML--chimera bcr/c-abl-gene, is detected on chromosome 22 or some other chromosome. It has been noted that only in rare cases of typical CML characteristic cytogenetic and molecular-genetic changes are absent. Further investigations should be conducted in the group of patients studied.

Experiments on white random-bred male mice were made to study the effect of L-thyroxine on cell proliferation of the hypotetraploid strain of Ehrlich's ascites carcinoma. It was shown that prolonged thyroxine administration (during 6 days of carcinoma growth) lead to synchronization of cell proliferation and the maximum values of the mitotic index was found 3 hours earlier then in the control experiments. At the same time thyroxine did not exert any noticeable effect on the average daily magnitudes of the number of DNA-synthesizing cells and did not change the pattern of modulations in the radioactive index. The changes in the mitotic index and radioactive index were asynchronous in control and experimental animals. Analogous results were found for hyperdiploid strain of Ehrlich's ascites tumor. Ploidy of cells did not influence the tipe rhythms of the cell proliferation and its reaction on the action of thyroxine.

Effects of native and recombinant interferons in normal and xeroderma pigmentosum (XP) human fibroblasts were studied. The criteria to evaluate the effects of interferons were: inhibition of replicative DNA synthesis, modification of replicative and unscheduled DNA synthesis in UV-irradiated cells. It was demonstrated that the level of inhibition of replicative DNA synthesis with interferons was dependent on proliferative status of cell cultures. The level of 3H-thymidine incorporation after stimulation of cell proliferation was increased in UV-irradiated normal fibroblasts pretreated with interferons. Interferon effect was not observed in XP cells. In cell cultures with low level of proliferation treatment with interferon resulted in inhibition of DNA replication and pronounced increase in the unscheduled DNA synthesis. In quiescent cells the effect of interferon on unscheduled DNA synthesis in UV-irradiated cells was not pronounced. In XP cells UV-irradiation induced low unscheduled DNA synthesis which was not modified by interferon.

Construction of a human cortex cDNA bank is described as well as the isolation from this bank of pBH71 and pBH3 clones with preferential expression in nervous and in tumor cells. The clones can be included into the third class of cDNA according to Sutcliff's classification. The mRNA corresponding to this cDNA class is considered to play the key role in determination of specificity of nervous tissue. Expression of the pBH71 sequence was revealed in human cortex and in tissues of different genesis (from neuroblastoma to uterus myoma), a 2 kb mRNA which corresponds to one and the same cDNA chain having been found in all tissues under analysis. The nucleotide sequence of cDNA insertion into the pBH71 clone of 447 n.p. was determined, and particular features of cDNA nucleotide composition and possible schemes of its translation were analysed. Weak homology was found between the 3'-end of cDNA insertion of the pBH71 clone and the 3'-end region of human proopiomelanocortine. The cDNA of the pBH3 clone hybridizes with the 0.8 kb mRNA revealed in human cortex and neuroendocrine tumors of different nature. No homology was revealed between the cDNA sequence of the pBH3 clone and any genes deciphered.

The results of myoma uteri family analysis are presented. Average estimates of family risks were: 26.6% for proband's sisters, 19.73% for proband's daughters (up to 44-years-old), 15.81% for proband's mothers. The estimate of heritability of the disease calculated according to the sibs data was 0.792 +/- 0.018, which points to the essential role of hereditary factors in the development of myoma uteri. The table of recurrence risk was calculated on the basis of the data obtained which may be used for forming risk groups in the course of mass physical examination.

Injection of 5-fluorouracil or caffeine or a combination of each of them with metronidazole removes partially or wholly the postirradiation arrest of DNA synthesis in Pliss lymphosarcoma and increases the label index and (or) the rate of its incorporation in nuclei of DNA-synthesizing cells compared to irradiated controls. The administration of the three agents arrests almost completely the DNA synthesis during the very first hours following irradiation, then prematurely removes partially the synthesis block in most DNA-synthesizing cells.

For the elucidation of the molecular basis of RSV adaptation to conditionally permissive host from the genome library of duck embryo fibroblasts, transformed by Rous sarcoma virus in 30 passages on these cells, recombinant bacteriophages that include provirus sequences, were obtained. Complete and transformation-defective proviruses were characterized, nucleotide sequences of their env-genes were compared with their counterparts the original RSV (Pr-RSV-C) and with viruses of other subgroups (A, B, D and E). The possible relation of the revealed changes in domains coding gp85 and gp37, with the changes of chicken RSV characteristics during adaptation to duck cells is discussed.

DNA repair synthesis and strand break DNA repair induced by 4-nitroquinoline-1-oxide and UV-irradiation in Xeroderma pigmentosum lymphocytes and fibroblasts pretreated by leucocyte interferons were studied. Stimulation of DNA repair synthesis in interferon-pretreated Xeroderma pigmentosum cells, defective in incision, was detected. No such effect was noted for strand break DNA repair. Hence, antimutagenic activity of interferons in human cells is connected with their modificating effect on DNA repair.

General and primary thermoresistance of mouse neuroblastoma clonal cell lines derived from N18A subline was studied: the N18A1 clonal cell line was not treated by heat, the NTR1 was obtained by one-step selection for resistance to the long action of the temperature 40 degrees C, the NHSR1 was obtained by multistep selection for resistance to short-time treatment at 44 degrees C. The NHSR1 clonal line was shown to have higher general and primary thermoresistance by comparison with that of N18A1 cells. The NTR1 cell line, capable of unlimited proliferation at 40 degrees C, did not differ in general resistance but displayed a slower primary resistance compared to that in the N18A1 cells. Cells of all the three clones were found to be capable of temporary increasing in primary thermoresistance, i.e. hardening. A possible contribution of the primary resistance into the general one in cells of all the selected clones has been discussed.

Analysis of DNA fiber autoradiograms from basal cell nevus syndrome (BCNS) skin fibroblasts has revealed for the first time a new defect in DNA replication earlier unknown in other chromosomal instability syndromes, that involves a significantly decreased rate of DNA-chain growth in unirradiated cells. Here we present evidence that the defect may be due to a marked reduction in number of simultaneously operating groups of replicons compared to that in normal cells, the rate of fork movement and the fusion of neighbouring units in the group remaining unchanged. Radioresistant DNA synthesis was observed in the BCNS cells. The exposure of cells derived from normal donor to gamma-rays at a dose of 5 Gy reduces the number of simultaneously operating groups of replicons to the level occurring in unirradiated BCNS cells, the rate of folk movement being unchanged in both cell types. However, the incidence of fusion between neighbouring units within the group is lower in the cells exposed to gamma-rays, due perhaps to a radiation-induced lesion in the group. Thus, ionizing radiation reduces the rate of DNA synthesis to the same level, however from different initial levels. Our data suggest that the phenomenon of radioresistant DNA synthesis may be explained by the presence of the initial defect in DNA replication in BCNS or any other chromosomal instability disorders.

A genomic copy of the mts271 gene which is specifically expressed in metastatic cells has been cloned and characterized. The gene consists of two exons and one intron and has an open-reading frame for the protein of 101 amino acids. The protein contains two helix-loop-helix calcium-binding domains, which is a common feature for the members of the large family of intracellular calcium-binding proteins (Ca B Ps). The primary structures of the mts271 gene products and other Ca B Ps were compared. High level of homology was found for S100 and calcium-binding protein of intestinal epithelium of rats. On the whole, the mts271 protein is a new calcium-binding protein which is specifically expressed in metastatic cells.

Microinjection of either type 1 human adenovirus, type SA7 monkey adenovirus virions or circular adenovirus DNA, obtained by the treatment of DNA-terminal protein complexes with glutaraldehyde, into nuclei of permissive cells results in the complete cycle of virus reproduction. Microinjection of neither linear native, condensed adenovirus DNA nor the DNA-terminal protein complexes under the same conditions initiates the adenovirus reproduction thought the synthesis of early and some late viral antigens is observed in the injected cells. Integration of injected adenovirus DNA into the cellular DNA occurs as far as 30 min after injection. Microinjection of either adenovirus DNA or its oncogene containing fragments into nuclei of semipermissive cells induces the transformation of these cells. In this case the time of the first appearance of transformation foci is decreased.

We have demonstrated that larval tissues of mutant stocks induced by injections of oncogene virus DNA (Sa7 and RSV) show the neoplastic mode of growth after transplantation into the body cavity of wild-type flies. Neoplasms tested were shown to be ordinary benign insect neoplasms, and at the same time they show the dominant mode of heredity typical of the neoplasms of vertebrates. Genetic factors responsible for the neoplastic growth are localised in the 3rd chromosome in the stocks obtained after injections of the adenoviral Sa7 DNA, and in the 2nd and 3rd chromosomes in the mutant stocks induced by the retroviral DNA.