A general principle of the maintenance of malignant growth in all types of tumors has been formulated. According to this principle, stochastic but continuous death of some tumor cells due to the inherent genetic instability of their genome (fragility of chromosomes) is the main event stimulating tumor growth. The dead cells trigger a complex multicomponent process of wound healing expressed as further proliferation of living tumor cells, angiogenesis, stimulation of cell migration, and other events. Stimulation of the proliferation of living cells leads to further death of cells and, as a result, to further stimulation of the system of wound healing, etc. Thus, the tumor sacrifices a small amount of dying cells to stimulate proliferation of all its other cells. It is proposed that the nature of the genetic instability of malignant cells is related to the appearance of an uninemic structure in some regions of chromosomes, in whole chromosomes, or in whole genomes. The author bases his statements on the binemic structure of chromosomes, which has already been experimentally and theoretically substantiated. Uninemic regions have an exceedingly high frequency of spontaneous chromosome aberrations due to blockage of the mechanism of underlying repair of the DNA double break in the absence of a second DNA copy. Possible approaches to a search for more efficient methods of therapy are discussed.

A study was carried out on the transcription regulation of the tag7/PGRP gene, whose product is similar to cytokines and is involved in recognizing peptidoglycane in mouse mammary adenocarcinoma cell lines KSML0, KSML100, and VMR-liver. The 3250-bp fragment of the promoter region was sequenced and tested for DNase I-hypersensitive sites (DHSs). In the KSML0 cells line, DHSs were found in the vicinity of the TATA box and approximately at position -3000 relative to the transcription start of the gene. Only a DHS cluster near the TATA box was found in the VMR-liver cell line. Regions involved in transcription regulation of the gene in the three cell lines were identified with the use of reporter constructions carrying the CAT gene under the control of deletion derivatives of the tag7/PGRP promoter region. The minimal promoter including only the TATA box with the nearest neighboring sequences was inactive in all cell lines. The elements (enhancers) positively regulating gene transcription in KSML0 and VMR-liver were mapped to region -192, -48. An element accounting for the transcriptional inactivity of the gene in KSML100 cells was assigned to region -315, -3250.

The results of study of morpho-cytochemical peculiarities, antigenic profile and peripheric blood and/or bone marrow blast cell karyotype of 21 patients with acute myeloid leukemia are presented. Hemopoietic cell immunophenotyping was carried out with the use of cytofluorometer FACScan and chromosome cytogenetic analysis with the use of analyzer "Metascan". It has been shown that in the AML M1 blast cell plasmatic membrane carries pan-myeloid CD33 and CD13 antigens, the last having high density of expression, and the CD38 antigen, which is a myeloid cell-precursor marker. In these patients tetraploidy, being the testimony of karyotype change, has been ascertained. It has been found out that the AML M2 blasts, except pan-myeloid antigens, express the cell proliferation CD71 marker. Blast cell karyotype peculiarities typical for this leukemia sub-variant have been revealed. In patients with the AML M4 in 3 of 6 cases an anomalous karyotype has been found. It has been also shown that the CD14 antigen, and rather its percentage in blast total population, is the differential-diagnostic criterion for the AML M4 and M5.

Results of comparative study of spontaneous and 5-bromdeoxyuridine-induced fragility of peripheral blood lymphocytes chromosomes in 9 patients with colorectal adenocarcinoma were presented. It was shown the increase of average spontaneous level of chromosomal fragility in patients with tumor aggregation in family as well as without it to 4.5 +/- 1.0 and 5.3 +/- 1.1 per 100 tested cells, accordingly. The increase of average level of damaged chromosomes in spectrum of rare sites to 12.5 +/- 2.6 in the patients with tumor aggregation in pedigree comparing to the patients without oncopathology in family 8.0 +/- 1.7 was observed. The most number of rare fragile sites was observed in 1q21 site of the chromosome 1. Possible connection between fragile sites of chromosomes in normal cells and malignant processes in the patients with colorectal cancer is discussed.

The effect of antitumor medicine Brotheophine to insertion of the marked precursors into DNA (14[C]-timidine), RNA (3[H]-orotic acid) and proteins (14[C]-leucine) of tumor cells (Pliss lymphosarcoma) as the indices of biosynthetic processes was investigated. It has been shown that Brotheophine acts as an antimethabolite of purine exchange and inhibits the vertical genetic information transfer in tumor cell (DNA-RNA-protein). Namely, a significant inhibition of 14[C]-timide insertion to DNA has been observed. less distinct is the inhibition of 3[H]-orotic acid to RNA und 14[C]-leucine to proteins. The above revealed allows to assume that during Brotheophine treatment certain changes in DNA biosynthesis take place leading to synthesis of slightly transformed RNA with subsequent impairment of proteins synthesis.

Data on lipid metabolism in 109 cases of endometrial carcinoma and 33 patients in control are presented. Relevant disorders were detected in 72.5% of the study group [stage I obesity--23 (21.1%); II--29 (26.6%); III--25 (22.9%); IV--2 (1.9%)] which was 1.5 times the mean level in controls (51.5%). The abdominal pattern of obesity was predominant (77.7%). Symptoms of cardiosclerosis were identified in 93 patients with endometrial tumors (85.3%), 93.5% of the latter group presenting with concomitant hyperglyceridemia. In 68.8% of endometrial carcinoma patients, incidence of arterial hypertension was higher than in controls (54.5%). Lipoproteins played a major role in dyslipoproteid pathogenesis involved in obesity and high blood pressure. A study of the insertion-deletion (I/D) polymorphism of apolipoprotein AI genes showed two deletion alleles (DD--6%) and one heterozygote (ID--3%) in control group; no deletion alleles were identified in endometrial tumor patients (0.1 (p(0.05). An investigation of the I/D polymorphism of angiotensin-converting enzyme genes identified deletion homozygotes in 30, insertion homozygotes (II)--27, and heterozygotes--41% (control). In endometrial cancer group, the deletion allele distribution was: DD--29; II--28 and ID--45%. Deletion allele frequency in control was 0.485 while in endometrial carcinoma--0.484 (p(0.05), i.e. with out significant difference.

This article generally reviews new original two-stage approach to an effective treatment of solid cancers by killing tumour cells by the activation of a prodrug after the gene encoding for an activating enzyme has been targeted to the malignant cell. The experimental data concerning gene therapy for malignant tumours by using oxazaphosphorines and cytochrome P450 in a novel combined chemotherapy/cancer gene therapy strategy discussed.

Some morphofunctional characters of fibroblasts in two genetic disorders--Cockayne syndrome (CS) and Basal cell naevus syndrome (BCNS) have been examined. The size of nucleus in BCN1SP line has been shown to be about 1.5 times less as well as the total size of nucleoli per nucleus, while the number of nucleoli was 2 times more compared with other cell lines investigated. Using the method of silver staining numerous nucleoli were shown to contain active loci of the nucleolus organizer regions. With the help of hybridization in situ the number of transcripts of 18S RNA molecules was shown to be 5 times more in BCN1SP cell line, and about 2.8 times more than in the other cell lines tested. The data obtained may be interpreted as a suggestion in favour of a greater activity of the nucleolus organizer regions in BCN1SP cell line followed by the disturbance in protein homeostasis of the cells.

BALD/c mice were injected, s.c., 1 mg 5-bromodeoxyuridine (BDU) on days 1.3 and 7 after birth and/or 0.1 ml 5% solution of urethane, 5 times a day every fourth day, i.p., at the age of 3 months. Lung tumors, mostly adenomas, developed in 67% of males and 56% of females, treated with urethane alone. Tumor frequency in response to BDU + urethane rose to 91% in males and 56% in females; multiple neoplasia increased too. In BDU-treated animals, lung tumors appeared in 13% of males and 25% of females whereas in intact controls-3 and 11%, respectively. DNA isolated from paraffin mounts of tumor tissue was used to identify mutations in codon 61 of Ki-ras oncogene. Polymorphism studies of restriction fragment lengths in PCR products failed to detect CAA CTA and CAA CGA sequence changes in 7 samples of DNA. Our findings do not rule out other mutations of RAS oncogenes in our material. They also suggest that further research focus on Ki-ras codon 12 as well as Ha-ras "hot" triplets.

L-MYC and GSTMI polymorphisms were studied in glioma patients. L-MYC allele frequency in patients (L: 61/114 (54%); S: 53/114 (46%)) and controls (L: 108/204 (53%); S: 96/204 (47%)) was identical. S allele was associated with certain unfavourable clinical features of the disease. In particular, its frequency was 26/42 (62%) in relapse vs. 26/68 (38%) in relapse-free disease (p < 0.05). GSTMI "null" genotype was identified in both patients and healthy donors (48%). GSTMI-deficient genotypes were significantly predominant in patients with grade III-IV gliomas as compared with grade I-II tumors (p < 0.05). Patients, but not donors, frequently revealed a combination of SS L-MYC homozygosity and GSTMI (-) variant (p < 0.01) as well as an association of LL L0-MYC homozygosity and GSTMI (+) genotype (p < 0.05).