Lymphoblastoid cell line was obtained from long-term human bone marrow culture. The cell line was characterized using methods of immunological phenotyping, cytochemistry and cytogenetics. This cell line represents different stages of B-cell differentiation, karyotype 46 XX. The cells of this line were able to support their growth during more than 10 months without exogenous stimulation.

Polyribosomes of Krebs 2 ascite carcinoma cells non-infected and infected with encephalomyocarditis (EMC) virus contain a heterogeneous population of low molecular weight small RNAs. Analysis of the RNAs by polyacrylamide gel electrophoresis did not reveal any qualitative differences in the small RNA sets within the composition of polyribosomes from virus-infected and non-infected cells. However, the content of one of the small RNAs was markedly elevated in polyribosomes from virus-infected cells. As can be followed from partial determination of its primary structure, this small mRNA is identical to 4,5S-RNAI previously detected in the nuclei of Novikov hepatoma cells of the rat. The data obtained suggest that 4,5S-RNAI can be involved in the regulation of protein synthesis in virus-infected cells.

A plasmid containing the bacterial gene of methotrexate-resistant dihydrofolate reductase (dhfr), under the control of early SV40 promoter, was introduced into murine teratocarcinoma CBA9H6 cells. From the whole pool of teratocarcinoma cells, which survived after transient methotrexate selection in vivo, the individual cells were isolated to give rise to 15 clones of tumors. Six of the 15 clones displayed nucleotide sequences of the original vector containing pBR322 sequences and the early SV40 promoter region; however, the bacterial dhfr gene was absent from the transformant clones. Possible causes of the loss of introduced dhfr gene from teratocarcinoma cells under non-selective conditions are discussed.

A new stable human hypernephroma cell line has been characterized by differential staining R-, C- and Ag-I-techniques. The karyotype of the cultivated hypernephroma cells has been designed using the statistical analysis and karyotype reconstruction methods. The specific chromosomal markers of the cell line are described.

The P388rm and P388rx cell lines resistant to antracycline antibiotics were obtained as a result of chemotherapy of mice bearing P388 leukemia, by means of increasing dosages of rubomycin and ruboxyl, respectively. These cell lines possessed cross-resistance to vinblastine, vincristine, colchicine, actinomycin D and some other drugs. Multidrug resistance (MDR) of P388rm and P388rx is due to decreased uptake of different cytotoxic compounds by the cells. Development of resistance to rubomycin and ruboxyl was accompanied by the appearance of additional chromosomal structures--long homogeneously staining regions (HSRs), double minute chromosomes and others usually containing amplified DNA sequences. Southern blot-hybridization with cloned DNA fragments amplified in Djungarian and Chinese hamster cell lines having MDR has revealed in P388rm and P388rx cells approximately 50-fold amplification of mdr and pC52 genes. Thus, in mouse leukemia cells which acquired MDR in vivo, as a result of chemotherapy, amplification is observed of the same genes that undergo amplification during selection of cell cultures for MDR in vitro.

A short review is presented concerning the studies developed in the Soviet Union during the last decade in molecular genetics of higher organisms, especially dealing with mobile genetic elements.

Chromatin fragmentation of bovine peripheral blood lymphocytes from normal animals and the ones suffering from chronic lympholeucosis (CLL) by DNase I, micrococcal nuclease and purified Ca/Mg-dependent endonuclease from nuclei of human splenocytes was studied. The lymphocytes chromatin from CLL animals was shown to be more resistant to nucleases, than the one from normal animals. It was found that difference between fragmentation of chromatin samples from normal and CLL bovines was more dramatic when Ca/Mg- dependent endonuclease was used versus traditionally exploited DNase I and micrococcal nuclease. The data suggest that purified Ca/Mg-dependent endonuclease can be a useful enzymatic probe for detection of lymphocytes chromatin changes during CLL.

Extrachromosomal closed circular IAP gene DNA was cloned from Ehrlich ascites carcinoma cells. Two clones were analysed in detain and the following conclusions were drawn: 1) there is closed circular IAP gene DNA in mouse cells; 2) the formation of circular DNA and the transposition of IAP gene by means of reverse transcriptase are documented.

Using centrifugation of the nucleoid in a neutral sucrose gradient, the damages in the secondary structure of DNA and the activity of repair enzymes, such as DNA-polymerases alpha and beta and poly(ADP-riboso) polymerase, induced by 1-methyl-nitrosourea (MNU) and 1.3-bis (2-chloroethyl)-1-nitrosourea (BCNU) injected at maximal nonlethal single doses to mice bearing parent leukemia cells (L1210/0) and resistant to MNU and BCNU leukemia L1210 cells (L1210/MNU and L1210/BCNU), were studied. The MNU-induced production of single-strand breaks in L1210/0 and L1210/MNU cells was more conspicuous in newly replicated DNA than in those in preexisting DNA. A more fast repair of the damages in newly replicated DNA was detected in L1210/BCNU and especially in L1210/MNU leukemia cells as compared with L1210/0 cells. The data obtained suggest that there are prone errors in the repair of DNA template, since most of the single-strand breaks were revealed in the newly replicated DNA synthesized on the repaired DNA. The repair of DNA damages in L1210/BCNU and especially in L1210/MNU cells was accompanied by the activation of DNA-polymerases alpha and beta and poly(ADP-riboso)polymerase. Both DNA-polymerases--alpha and beta--were shown to be involved in repair of DNA damages induced by MNU and only DNA-polymerase beta was involved in the repair of damages induced by BCNU.

Data are reviewed concerning the results of study of multidrug-resistant (MDR) tumor cells. MDR often develops in the course of chemotherapy or in vitro selection of tumor cells by vincristine, adriamycin, actinomycin D, colchicine, etc. MDR cells are resistant to all these drugs though their targets and mechanisms of toxic action are quite different. Resistance is due to the decreased accumulation by MDR cells of these compounds. The genetic basis for MDR is amplification of a large genomic region that contains a number of genes coding for products and functions that are under extensive study. Specific karyotype and amplified DNA alterations occur during the development of MDR imitating the processes of appearance and variability of multigene families. The obtained data demonstrate the ways of overcoming of tumor multidrug resistance in clinic.

Immunization of DMBA-treated mice by the glycoprotein fraction from mammary glands of mice BALB/c did not decrease the frequencies of induction of mammary tumors. This is in contrast to the results obtained during immunization by the formaldehyde treated preparation of Mouse Mammary Tumor Virus (MMTV). EcoRI and HindIII cleaved DNA from the DMBA-induced mammary tumors did not contain the additional virus specific fragments. In mammary tumors the expression of p27 MMTV was registered in contrast to normal mammary glands and mammary epithelium cultures in which the proteins of MMTV are not expressed even after induction.

The results of Mendelian analysis of the hereditary colon polyposis are presented, considering age influence on manifestation of the character and specificity of the data obtained. The possibility of pleiotropic monogenic control of the hereditary polyposis and primary colon cancer is checked up and confirmed.

The data on localization of heritable fragile sites and cellular oncogenes on individual human chromosomes involved in tumour-specific aberrations are summarized in the review. Only two fragile sites (8q22 and 11q13) out of eight ones, coinciding with breakage sites in such aberrations are the loci of cellular oncogenes (mos and bcl-1, respectively). Analysis of the data confirms the supposition that heritable fragile sites are predisposing factors for chromosomal rearrangements and in the end for development of the pathological processes.

It is shown that the average number of sister chromatid exchanges (SCE) per one cell in patients with tuberous sclerosis as well as in those with Recklinghausen's neurofibromatosis do not differ from the control. But the non-parametric methods of analysis have revealed differences in the spontaneous level of SCE is patients with tuberous sclerosis, while no such differences were revealed in patients with Recklinghausen's neurofibromatosis.

The extent of methylation of MspI-HpaII sites of alpha-fetoprotein (AFP) gene in DNAs from normal rat livers, rat hepatoma cell lines and their clones was compared by Southern blot hybridization. The expression of this gene was controlled by measuring the level of AFP specific RNA and by immunoperoxidase staining with antibodies to AFP. It was found that the AFP gene contained several CCGG sites in the 5'-region methylated in the nonproductive cell lines and normal adult liver and undermethylated in productive cell lines. The same phenomena was observed for productive and nonproductive hepatoma McA-RH7777 clones. These findings suggest that specific changes in the methylation pattern are associated with changes in AFP gene expression.

Del(8) (q24.11-q24.13) were detected in 3 patients with typical Langer-Giedion syndrome (LGS) and studied by high-resolution methods. Analysis of the literature strongly suggests the chromosomal ethiology of the LGS, because in all patients examined in detail a deletion of the segment 8(q24.11-q24.13) was revealed, which is critical for the LGS. Interrelationships between the LGS and two monogenic conditions-tricho-rhino-phalangeal syndrome type I and multiple exostoses are discussed. The possible role of c-myc oncogene in exostoses' (including those in LGS) origin is anticipated.

It has been shown using labelled modified AO cytofluorometry of DNP cellular thermal denaturation that the melting profiles of peripheral blood cellular chromatin in children with acute lympholeukemia (ALL) were of strictly individual, "unclassifiable" nature and were similar to those of their mothers but different from those of their fathers and healthy people, which seems in favour of a possible connection between the disease under study and the peculiarities of the mother's genotype. Similar types of deviations have been found in the structure of interphase chromatin of healthy parents of children with ALL. Such a combination of changes in the parents' genotype may prove unfavourable, increasing the birth rate of neonates with a genetic predisposition to the disease in question.