Using DNA fiber autoradiography, DNA replication in cultured fibroblasts, derived from normal donors, and from XPII patient with increased sensitivity to ionizing radiation was estimated. Here evidence is provided on the fact that the fork movement, significantly decreased in XPII cells before irradiation, remains the same after exposure to X-rays. The density of replicon clusters simultaneously operating in tandem groups, which is initially much less in XPII cells compared to normal cells, also remains unchanged after exposure to X-rays (5 Gy), since the inhibition of DNA replication occurs to individual replicons only. Our data suggest that the inhibition of DNA replication in normal cells throughout the whole cluster, that drastically reduces the rate of DNA-chain growth, may provide an additional time to restore damaged chromosomes, i. e. it is part of the cellular defence mechanism. It seems likely that XPII cells are deficient in such a defence mechanism.

Nucleotide particles, resulting from mild lysis procedure, obtained from two strains of murine L5178Y lymphoma cells, differing in radiosensitivity (L-R and LY-S) showed differences in the sedimentation rate and in the halo rewinding in the presence of 40 micrograms/ml Ethidium bromide (EB). Microgel electrophoresis of DNA after an exhaustive lysis of cells (in the presence of sodium laurylsarcosine and proteinase for 20-24 h at room temperature) disclosed not only heterogeneity in DNA migration length among LY-R cells (LR) and LY-S cells (LS), but also differences between two strains with respect to this parameter. L-value for LY-S cells exceeds that for LY-R strain by 20 per cent, and the ratio LS/LR remains constant regardless of the voltage applied. Thus, the cell distribution pattern according to L-value is the intrinsic parameter for both LY-R and LY-S cells, and DNA of LY-S cells is suggested to bear more background strand breaks as compared with the radioresistant LY-R cells. LY-R cells irradiated with 10 Gy repair their DNA completely after 60-90 min of incubation at 37 degrees C but DNA migration pattern for irradiated and repaired LY-S cells is characterized by the predominance of DNA with a higher L-value than that for intact cells. Hence, we suggest that the higher radiosensitivity of LY-S cells might be compatible with a relatively high background DNA breakage in these cells.

Specific small ribonucleoprotein (alpha-RNP) complexes have been identified and characterized in the human epidermal carcinoma A-431 cells. The alpha-RNP complexes contain Alu-homologous small RNA, along with other small antisense RNA species. The epidermal growth factor (EGF) has been shown to induce selective specific changes in the expression of the small alpha-RNAs, the expression of the Alu-like RNA being repressed. Specific changes in the protein composition of the alpha-RNP complexes have been detected under the influence of EGF.

Oncogenesis in transgenic mice is at present a model, most adequately reflecting the natural conditions of tumor development. One of more important traits of this model is that it allows to study malignant growth simultaneously at all the structure-function levels in the context of the whole organism. This paper is a review of results of a series of experiments in which the localization of tumors was dependent or independent on the tissue specificity of a promoter, as well as development of multiple tumors with the use of viral regulatory sequences in genetic constructions. It has been shown that although a transgene is expressed in most of the tissues, tumors develop in some particular tissues only. These observations are interpreted by some authors in favour of the concept of multistep cancerogenesis. In this view, of primary importance are the results of studies on oncogenesis in transgenic mice, which contradict this concept and are regarded by their authors as an evidence of the possibility of a one-step transformation of normal cell into malignant one. The analysis of the obtained material enabled us to put forward an assumption that the key role in oncogenesis is played not only by certain genetic disturbances, but also by multi-level homeostatic mechanisms. Apparently, it is just the transgenic mice with cellular or viral oncogenes in their genome that represent a more adequate model for the detection of certain molecular-biological mechanisms underlying these disturbances. Also, of much importance is abundant material accumulated by now on oncogenesis of transgenic mice which shows a possibility of the effective use of various genetic constructions with prokaryotic and eukaryotic regulatory sequences, a possibility to induce not only tumors of some particular tissues, but also multiple hyperplastic and neoplastic changes in one and the same mouse. Development of tumors in such transgenic mice can be regarded as a model of different types of cancer disease.

A human insulinoma cDNA library was constructed in the expression plasmid vector pUEX1. The clone pUEX1Ins12 was selected by means of hybridization with an insulin probe. It codes for full size amino acid sequence preproinsulin. The bacterial strain pUEX3Ins8 producing proinsulin as beta-galactosidase fusion protein was obtained for the use of recombinant protein as an antigen in an ELISA to detect serum antibodies in subjects with IDDM. Recombinant clones containing the middle, N- and C-terminal domains of the GAD65, the major autoantigen in IDDM, were constructed in pVEX1. These clones may become important tools to study the nature of GAD autoreactivity in IDDM. The clone pHICEO.9 was selected from the human insulinoma cDNA library by immunoscreening with total human insulinoma protein antibodies. This clone expresses the C-terminal fragment of human cholesterol esterase/lipase containing its antigenic determinant and can be used for blood lipase determination. Four clones containing cDNA inserts (0.47-1.42 kb) without any significant homologies to the known sequences in the Gene Bank were obtained by means of statistic selection.

Specific features of metastatic spreading of lung cancer have been compared in 258 surgical patients from families with a history of lung cancer incidence (group I) and in 861 controls (group II). Lesions in lymph nodes at various stages were more frequent in group I, metastatic spreading incidence increasing in step with stage. In is noteworthy that more frequent lesions in mediastinal lymph nodes (stage IV) were observed in group I (54.2%), as compared with 11.8% in controls (P < 0.001). Multiple lesions of lymph nodes at all stages of metastatic spreading featured prominently in 48.5% of group I, as compared with 17.0% in group II (P < 0.001). Metastatic spreading was studied versus such characteristics of primary tumor as size, histologic pattern and pattern of tumor growth.

Seven spontaneously transformed cell lines LREC of rat embryo fibroblasts were obtained by an originally elaborated cloning technique (method 2T7). Six lines (1-6) were obtained from Rattus norvegicus cells, and one line (LREC-7) from Wistar rats. Method 2T7 was based on a serial propagation of rat embryo cells, brought to a "crisis" stage under conditions of a higher cell density and followed by the appearance of actively proliferating cell clones. These lines were analysed cytogenetically at the earliest stages using the Giemsa G-banding technique. In the karyotypes of six LREC (1-6) lines two abnormal chromosomes 7 were revealed: one marker chromosome M1-t(7; 19) results from translocation between chromosomes 7 and 19, the other marker chromosome M2--del(7) is a result of deletion of the second homolog of chromosome 7 in the q11.2 q22.1 loci; besides an extra normal homolog of chromosome 7 was revealed. There are only two marker chromosomes M2 in the LREC-7 line karyotype. Cells of LREC (1-3) lines could be transformed from the immortalized stage to the malignant one by the 30-45th passages. The cells of LREC (4, 7) lines became malignant at the 10-8th passages, resp. The rearrangements of chromosome 7 are supposed to be specific for LREC lines obtained by our method. A hypothesis is put forward that the translocation of chromosome 7 may play an important role for the immortalization of the rat embryo cells. The deletion of chromosome 7 may be associated with a malignant transformation of cells, as it is possible that the deleted loci have a recessive oncogene. Method 2T7 allows to obtain constantly spontaneously transformed cell lines of rat embryo cells with the least abnormal karyotype.

DNA was assayed in cell nuclei of squamous-cell carcinoma of the tongue (35 cases) and mucosa of the oral cavity fundus (15) using flow cytometry. The measurements were made versus size of tumor, cell differentiation stage and presence of metastasis to regional lymph nodes. Aneuploidy incidence was found to be in direct correlation with tumor size, low cell differentiation and ability to disseminate.

The comparative analysis of frequency of occurrence of different indications of cytogenetic variabilities in blood cells of cattle groups (relative healthy, infected by bovine leukosis virus and exposed to ionizing radiation in the Chernobyl zone) was carried out. Both genotoxic influences induced increases in frequencies of cytogenetic defects, but only ionizing radiation induced the increase of chromosome aberration frequency. The heterogeneity of all cattle groups for investigated cytogenetic characters was revealed.

Natural leucocyte interferon (IF) upon injection to two patients affected with Xeroderma pigmentosum for three weeks stimulated the inhibited DNA replication and Host reactivation at the level of healthy donors. Tigasol--the drug used traditionally for the treatment of diseases caused by Xeroderma pigmentosum proved less effective than IF.

For investigation of FMS gene polymorphism and mutations that reveal functionally meaning in leukemia and myelodysplastic disorders the overlapping recombinants lambda-clones inserted by FMS gene fragments have been obtained from human leukocyte genomic library in the EMBL 3A phage by using oligonucleotide prode (27 nucleotides) based on 12 exon of the FMS gene. 15 DNA probes were prepared by subcloning the lambda-clones obtained in the pBSKS+ plasmid. The probes obtained allow to analyse extracellular, transmembrane and tyrosine kinase regions of the FMS gene independently.

Protein-DNA complexes released from chromatin of the intact rat liver and hepatoma induced by N-diethylnitrosamine during nuclease digestion have been subdivided into two groups of high and low molecular weight. Immunoreactive proteins are concentrated mainly in high molecular complexes. Immunoblotting of proteins from the nuclease-sensitive regions of normal and tumor chromatins allow distinguishing antigens of three main types: 1--antigens of nuclease-sensitive samples common both for normal and tumor cells; 2--antigens determined in tumor preparations only; 3--antigens usual for normal samples. Such differences in composition of immunogenic proteins in the nuclease-sensitive regions from the cells of the normal and malignant rat liver may be useful for investigating changes in active chromatin during chemical induction of tumors in animals.

Radiation multigeneration carcinogenesis' mechanisms are associated with inheritance of non-specific genome lesions. Evidence indicates that the effect is significantly enhanced by some chemical carcinogens action on the offspring of irradiated parents. Hereditary character of the phenomenon is a prerequisite to accumulation of these genetic determinants in the population. The risk of radiation multigeneration carcinogenesis for man could be as much as 0.4 x 10(-2) Sv-1 over one generation.

The paper presents information on fundamentals of oncogenetics, role of the clinical and genealogical method in oncology, in epidemiological genetics in particular. It is shown necessary to create registers of family cases of tumours proceeding from genetical data: risk groups on appearance of malignization. The ways for the further study of the role of a hereditary factors in tumour growth are outlined.

The paper presents results of investigation of constitutive heterochromatin of chromosomes 1, 9 and 16 in 23 patients with endometrial cancer and 5 women of the control group. The analysis was carried out on slides obtained by the routine method of the peripheral blood cell culture. The C-band segment variability was studied by the C-binding method. The investigation established an increase of polymorphism of constitutive heterochromatin in cancer patients, extreme variants and heteromorphism of homologues of chromosomes 1, 9 and 16. It is shown that polymorphism of the C-band on chromosomes 1, 9 and 16 in patients with cancer in their families increases as compared to the patients without cancer pathology in pedigrees.

The induction of mutations to 6-thioguanine-resistance and chromosome aberrations by the plasmid pSVc-myc-1, carrying the activated cellular oncogene c-myc, isolated from a mouse plasmocytoma was studied in a cultured Chinese hamster cell line. The yield of HPRT- mutants and chromosome aberrations increased 1.6 times on the average after pSVc-myc-1 treatment. The mutagenic activity of pSVc-myc-1 was statistically significant. The role of mutagenic effects of activated cellular oncogenes in malignant transformations is discussed.

Amplification of oncogenes erbb-2, erbb-1, c-myc and losses of heterozygosity (LOH) at chromosomes 11p (probe hras-1), 17p (probe ynz-22) and 17q (probe thh-59) were studied in 165 human tumours (60 breast, 22 ovary, 40 colorectal, 23 lung, and 20 thyroid carcinomas). The correlation (P < 0.01) between the increased copy number of mentioned oncogenes and LOH at 17p was demonstrated for tumours tested: extra copies of these oncogenes were revealed in 11 of 46 DNA specimens with LOH on ynz-22, but only in 3 of 61 without LOH. This correlation was mostly due to frequent combinations between erbb-2 amplification and 17p deletions; the incidence of increased copy number of erbb-1 and c-myc oncogenes was not high enough for final conclusions about the association of their alterations with LOH at chromosome 17p.