Antitumor and cytogenetic activities of 4-epi-doxorubicin (EDR), an anthracycline antibiotic, were studied on female Wistar rats with transplantable ascitic ovary tumor (OT). It was shown that after a single administration in a dose of 3 mg/kg, EDR prolonged the average lifespan of the tumor-bearing rats by 213.4 per cent as compared to that in the controls. The maximum number of the aberrant cells in the bone marrow was observed 24 hours after injection of EDR. In 6 day it decreased to the control level. The maximum increase in the number of the OT aberrant cells was recorded 2 days after EDR injection and even in 10 days the number of the aberrant cells amounted to 20.2 +/- 1.3 per cent. It is suggestive of a high selective action of EDR and relation between the EDR antitumor activity and the disturbances in the chromosomal apparatus of the OT cells.

Rearrangements of genetic material in the peripheral blood lymphocyte nuclei have been found in patients with dysplastic pigmented nevi and malignant melanomas (15 cases), in contrast to the control (10 healthy persons). It is expressed as an increase in the number of chromosome aberrations in the karyotype and as a change of the Feulgen-positive substance correlation in the interphase nuclei of the given cells towards an increase in the active-functioning DNA structures.

The transcription of genes c-myc and hsp70 following inhibition of plasmacytoma cells proliferation by glucocorticoid hormone dexamethasone has been investigated. The dynamics of [3H] thymidine incorporation into the plasmacytoma cells DNA after incubation with dexamethasone has been studied. It declines after 8-35 h incubation with dexamethasone. The transcriptional activity of c-myc gene decreased after 3-12 h of incubation with hormone and restored to the original level at 24-30 h. The level of transcription of hsp 70 gene decreased after 12-48 h of introduction of hormone. Heat-shock treatment resulted in decrease of c-myc expression and to some increase of the transcription of hsp 70 gene. So, the dynamics of transcriptional activity of the genes c-myc and hsp70 are different and independent.

The review deals with analysis of the literature data concerning the importance of valine substitution in certain proteins, namely p21 ras and hemoglobin. A model of the active site of p21 protein is discussed in the light of GTPase activities alterations as a result of monoaminoacid substitution in conservative sites of p21 protein. The established relationship between some forms of transformation and Plasmodium falciparum malaria on the molecular level is shown in a new aspect. The widespread opinion that Hb S is valid as the means of malaria resistance is questioned in terms of new molecular data.

The hybridoma genomes contain polyploid sets of immunoglobulin genes. We have shown, that the hybridoma PTF-02 genome contains three genes of heavy chains and two genes of light chains. The genes responsible for antibody synthesis were cloned and their structure were determined. Investigation of the kappa gene transcription and its fragments which contain regulatory sequences revealed a nuclear factor. The latter interacts with the octanucleotide localized at the promoter region of the kappa gene. The purified factor activates the transcription of the kappa gene in a heterologous cell-free system. Together with the tissue-specific factor there is also an universal factor interacting with the octanucleotide sequence. We have shown an additional factor in lymphoid cells interact with the protein which binds to the octanucleotide sequence. We have shown an additional factor in lymphoid cells interacting with the protein which binds to the octanucleotide sequence. As a result, there is a family of factors which interact with ATTTGCAT sequence. One major factor (m.w. 60 +/- 2 kDa) is an obligatory component for the initiation of immunoglobulin genes transcription.

The c-Ha-ras-1 locus in 84 cancer patients was examined for allelic restriction fragment length's polymorphism, as well as for distribution of four common c-Ha-ras-1 alleles (a1, a2, a3 and a4) in lung, ovarian and thyroid cancer patients. In approximately half (8 out of 15) lung and ovarian carcinomas possessing a4 allele, alterations in the Ha-ras locus (deletion, amplification and change in allele length) were detected, as compared to 2 cases of rearrangements out of 40 tumors lacking the a4 allele. An increased a4 allele frequency was found in individuals with lung and ovarian carcinomas, as compared to both controls--summarized literature data, and thyroid cancer patients. On the other hand, homozygosity for the a2 locus, resulting from deletion in another allele, and increased a2 allele frequency in thyroid cancer patients were observed. Thus, a4 and a2 alleles of the c-Ha-ras-1 may perhaps be viewed as genetic markers of predisposition to lung, ovarian and thyroid cancer, respectively, in combination with other clinical parameters.

An analysis of clinical and family history of 36 patients with endometrial cancer revealed clustering of tumors in some families. Cytogenetic studies of peripheral lymphocytes showed increased counts of aberrant cells in patients with endometrial cancer as against their values in normal women and patients with endometrial hyperplasia.

Activated human Ha-ras oncogene cloned on the plasmid pEJras6,6 was transfected into REF (LT) cells immortalized by the gene for large T-antigen of the polyoma virus. The cells were shown to become completely transformed (in the terms of morphology and tumorogeneity) only after three cycles of transfection with the plasmid pEJras6,6. The integrated sequences of the plasmid pEJras6,6 and the ras oncogene product p21Ha-ras were detected in cells only after their selection in the nude mice (in the cell culture REF (LT) ras X 3tu obtained from the tumor and directly in the tumor cells). Thus, after sequential transfections with a c-Ha-ras oncogene we developed cell cultures on the different stages of transformation process.

Hepatitis B virus (HBV) is the causative agent of hepatocellular carcinoma (HCC) in man. The HBV genome is a circular partially double-stranded DNA molecule of about 3.2 kb. The HBV genome contains four structural genes coding for the HBV envelope (HBsAg) and core (HBcAg/HBeAg) proteins, endogenous DNA-polymerase with the additional enzymatic activity of a reverse transcriptase and polypeptide X functioning as a trans-activator of cellular and viral genes. HBV DNA integration in the genomes of HCCs and hepatocytes of HBV carriers is an important evidence establishing a relationship between the HBV infection and the development of HCC. The mechanism of HBV DNA integration into the cellular genome and the possible role of integrated HBV DNA sequences in the malignant transformation of hepatocytes are discussed.

The data on the changes in the isoenzyme spectrum of pepsinogen-pepsin inversely correlating with the development and retaining of the malignant condition of gastric mucosa in human and animals are reviewed. The results of the molecular-genetic studies of gastric carcinogenesis, in particular the role of protooncogenes--oncogenes in this process are presented.

The intracellular Na+/K+ ratio was studied for its effect on expression gene beta-actin and oncogene c-fos and activity of these genes during the mitotic cycle in ascites cells of leukemia P-388 and Ehrlich tumour. It was established that gene beta-actin was activated at high and low ratios of Na+/K+, while c-fos only at high ones. The expression of these genes during the mitotic cell cycle was due to changes in the intracellular Na+/K+ ratio. The obtained data showed an important role of intracellular homeostasis of monovalent cations in regulation of gene expression during the mitotic cell cycle.

No correlation between the sensitivity to induction of liver tumours by ortho-aminoazotoluene and predisposition to spontaneous development of these tumours was found in mice. Under crossing the predisposition to spontaneous tumours was inherited dominantly, while sensitivity to their induction was inherited by the intermediate type. Spontaneous hepatomas were more frequent in males, whereas induced onesin females of the same genotype.

Karyological analysis of 6 lines with distinct tumorigenic properties of mouse strains C3H/He and C57BL/6 has been carried out using a differential staining of chromosomes. The number of normal copies of chromosomes varied in all the investigated cell lines. The more and the less stable chromosomes different from line to line. All the cell lines were characterized by decreased numbers of copies of normal chromosome 7; a decreased number of normal copies of chromosome 2 and 16 was detected in the course of the cell spontaneous neoplastic evolution. The decreased number of normal copies of chromosomes 8, 12 and X, and the increased number of normal copies of chromosome 10 were specific of the cell lines with intermediate tumorigenicity. The maximum tumorigenic cell lines differed from all other lines by increased numbers of copies of chromosomes 4 and 5, and by a decrease in copy number of chromosome 6. The data obtained are discussed in terms of the search of the regularity of karyotypic changes in the course of the cell neoplastic evolution.

The structure and composition of the nuclear skeleton (nuclear matrix) are considered. The literature data are referred to and the findings of the original author's research on the associations of the nuclear matrix with DNA, its involvement in the control of replication and transcription occurring on the nuclear matrix sites. Special attention is given to the protein composition of the nuclear matrix, and to its changes in tumour growth, virus infection, as well as during mitosis and embryonal development.

The intracellular Na+/K+ ratio was studied for its effect on histone genes expression in Ehrlich carcinoma and leukemia P-388 ascites cells. After equilibration with certain Na+/K+ ratio buffers at 0-4 degrees C the cells were treated during 1 h at 37 degrees C with ouabain added to the corresponding medium. Then total RNAs were extracted and analyzed by the reaction of blot-hybridization with histone genes cluster in plasmid p604. The maximal level of histone genes expression in leukemia P-388 cells was observed under conditions when intracellular Na+/K+ ratio corresponded to those at S-phase of the mitotic cycle. In Ehrlich carcinoma ascites cells the expression of histone genes was not dependent on the Na+/K+ ratio. A conclusion is drawn that the intracellular ratio of monovalent cations is one of the possible mechanisms which regulates the gene expression during the mitotic cycle.

The ribosome content (84 patients), DNA alkaline-labile sites or strand breaks (21 patients) and unscheduled DNA synthesis in lymphocytes under normal and B-cell chronic lymphocytic leukemia (B-CLL) were studied. It has been shown that the alkaline-labile DNA damages increased about 3-5 fold while the ribosome content was normal at an early (corresponding to Rai's O-I stages) and an advanced (II-III stages by Rai) stages of B-CLL. In the course of B-CLL, the DNA strand breaks and number of ribosomes per cell decreased with the correlation coefficient r = 0.72. The slowing down of the unscheduled DNA synthesis at the advanced and terminal (IV stage by Rai) B-CLL stages does not correlate with the DNA strand breaks. In the advanced stage with its established clinical variability of forms, when an adequate treatment was necessary, the lymphocyte ribosome levels drop following the expansion of main compartments involved by the leukemic spread.

Frequency and spectrum of chromosomal aberrations were studied in hemopoietic cells of Wistar rats myeloid leukaemia induced by the prolonged exposure to tritium oxide. Differences in quantitative and structural damages of chromosomes were revealed by the cytogenetic assessment of eighteen rats with acute myeloid leukaemia (AML) and six rats with chronic myeloid leukaemia (CML). The most characteristic chromosomal aberrations for AML appeared to be rearrangements in chromosomes 1-3. In CML translocations by one of chromosomes 15-20 coupled with defects in the groups of chromosomes 5-10 seemed to be nonrandom.