In the present paper we have shown that JB6 and PDV murine skin carcinoma cells, as well as previously described sarcoma B6-4 cells, can revert to a nontumor phenotype. Revertant carcinoma clones could not grow in soft agar conditions and like sarcoma revertants acquired dependence on peptide growth factors, and exhibited a reduced expression of c-jun. Spontaneous revertants were shown to be instable. They could revert back to a transformed phenotype in 1-5 months of in vitro passaging. Being inoculated in syngeneic animals, these transformed cells show a recurrence in 2-5 months, similar to that of a dormant metastasis. Thus, dormant revertant cells are believed to be included in many tumors of different origin. So, spontaneous reversions of tumor cells may play an important role in the dormant metastatic process. The cause of these frequent spontaneous transient reversions and revertant instability appears to be of epigenetic nature. Causes and mechanisms of cell transformations and reversions remain to be clarified.

Due to immunophenotypic examination of bioptic samples from 30 patients with non-Hodgkin's lymphoma (NHL), malignancy of B-cell NHL was identified at an early stage of diagnosis, before histological analysis yielded the results. Negative expression of T-cell antigens, monoclonal character of light-weight chains of immunoglobulins, positive expression of B-cell antigens and marked expression of CD5+ are immunologic markers of low-malignancy B-cell NHL. A similar immunophenotypic pattern, involving negative expression of CD5- and positive one for Calla-antigen as well as one identifiable by monoclonal non-cluster antibody IPO3, is a marker of highly-malignant B-cell NHL.

The gene coding for p53, a suppressor of malignant growth, is induced by various stress factors that cause appearance of the hereditarily pathologic cells. One of important p53 functions is initiation of apoptosis that eliminates potentially dangerous cells from the organism. The mechanism of p53-induced apoptosis are reviewed.

The results of analysis of interloci associations between two pairs of syntenic loci (transferrin and ceruloplasmin, receptor for vitamin D and kappa-casein) and two non-syntenic ones (amylase-1 and post-transferrin 2) in two cattle groups of Red Steppe breed (infected and uninfected by bovine leukosis virus) and in two groups of Black-and-White Holsteins (from relatively "pure" zone and from the 10 km zone of Chernobyl NPP) were presented. It is found that "linkage disequilibrium" between loci is observed independent of their synteny. The data obtained allowed the authors to suppose, that the interloci associations are rather controlled by different factors of artificial and natural selection than by the genetic linkages between genes.

Flow cytometry was used for measure DNA content of tumor cells of squamous-cell carcinoma of the tongue and mucosa of the oral cavity fundus, invasive ductal breast carcinoma, endometrial, colonic and rectal adenocarcinomas. Frequency of aneuploidy is characteristic of tumor. Frequency of aneuploidy is high in the oral cavity and breast cancer, colonic and rectal carcinomas and low in cancer of the tongue and endometrium Aneuploidy is associated with nonfavorable clinical and morphological signs of breast cancer, carcinomas of the oral cavity, corpurus uteri and rectum. High DNA index is typical of aggressiveness of carcinomas of the tongue, breast and endometrium. High proliferative activity prognostic factor of endometrial adenocarcinoma. We also found aneuploid cells in normal epithelium of the corpurus uteri, colon and rectum of patients with aneuploid tumors of the same organ. It is possible to suggest that these cells is an unfavorable cause recurrence.

Race is widely believed to be a factor in the relationship between S allele of L-MYC oncogene and disseminated lung cancer. In particular, the clinical significance of L-MYC genotype was demonstrated in the Japanese while the results for the white US, Australian and Norwegian cohorts were negative. The present study was concerned with distribution of L-MYC oncogene alleles in 43 patients with lung cancer and 77 healthy subjects in Moldova. L and S allele frequency in both groups were nearly identical. However, the SS genotype was registered much more frequently in patients with metastasis (10/28; 36%)(p < 0.05) than in those with localized tumor (0/12). Moreover, overall frequency of S allele was significantly higher in lung cancer patients with node involvement (35/56; 63%)(p < 0.02) than in those with localized tumors (8/24; 33%)(p < 0.02). Finally, a significant correlation was found between S allele occurrence and distant metastases (M1: 19/28; 68%; M0:26/58; 45%)(p < 0.05). Similar data were reported in Russia. (ABSTRACT TRUNCATED)

An abnormally long shorter shoulder of chromosome 21 was identified in 3 out of 4 members of a family at high risk for gastric cancer. We attempted to clone the amplified fragments of DNA of one of the family members who had the same chromosomal marker. This was done after the amplified sequences were enriched by re-association in phenolic emulsion, and 52 clones were obtained. All inserts were separated and each was hybridized on filters containing Hind III DNA of patient O.L. and that of a healthy donor. Hybridization with the genome DNAs of patient O.L. and the donor failed to go through in 9 inserts. Hybridization with all genomic DNAs went through in 34 inserts. Hybrids with one or several Hind III fragments of DNAs of O.L. and the donor were formed in 9 inserts. The size of fragments with varying molecular weight in inserts 6, 9, 11, 30, 39, 43 and 44 identified in the DNA of patient O.L. was 3-10 times that in the DNA of the donor. The differences in the molecular weight and size of the detected bends seem to indicate that we succeeded in cloning at least several different amplified fragments of the genome of the patient.

Expression of cysteine proteinases, cathepsins L and B, and their inhibitors was studied out in three model systems of rat embryo fibroblasts, sequentially immortalized and transformed by different genes. In Model I rat embryo fibroblasts were immortalized with DNA of early region of simian adenovirus SA7 (clone REF-1) and then transformed by c-Ha-ras oncogene (REF-2EJ; malignant transformation). In Model II and III, the immortalized fibroblasts (clone IE5) were obtained by transfection with the polyoma virus LT gene and the clone IE5 used lost this gene; the malignant transformation was achieved by transfection with the E7 gene (clone trF8; Model II) and E6/E7 genes ¿clone A5E5(pC7-1); Model III]¿ of human papilloma virus types 16 and 18 respectively. In Model I, the increase in the total cathepsin L and B activity was correlated with the stages of transformation, at the same time, in Models II and III, this activity in immortalized IE5 fibroblasts was higher than at transformation stage. The activity of cathepsin L in lysates of transformed fibroblasts--REF-2EJ, significantly exceeded this activity both in transformed cells trF8 and A5E5(pC7-1)(6- and 10-fold, respectively). In cell cultures of Models I and II, the increases in secreted activity of cathepsins L and B were correlated with the stages of fibroblasts transformation, but in cultures of Model III, this activity at the stage of malignant transformation was lower than that the stage of immortalization. Therefore, the activities of cathepsins L and B were expressed to varying degrees at different stages of oncogenic transformation and the expression of their activities were dependent on type of transforming gene. It was established that changes in proteolytic potential were correlated with differences in the transforming phenotype of cell clones. An endogenous inhibitor(s) of cysteine proteinases was found in conditioned media of all type cell cultures. Expression and inhibitory properties of this inhibitor(s) were different at distinct stages of transformation.

Cell clones of the finite organospecific rat rhabdomyosarcoma RA-23 were selected in vivo for high and low frequency of interphase cells with chromosome bridges. After selection for high frequency of cells with bridges, the frequency of cells with anomalies of nuclear form sharply increased in the cell populations. These anomalies were manifested by long nuclear protrusions into the cytoplasm. This type of anomaly was termed tailed nuclei. In the studies populations of RA-23, the frequency of cells with "tailed" nuclei positively correlates with the frequency of interphase cells with chromosome bridges and the frequency of ana- and telophases with chromosome bridges. These parameters might be genetically associated: dicentric chromosomes form chromosome bridges in ana- and telophases of mitosis. Then, in some cases, the bridges are maintained, which result in the appearance of interphase cells with bridges, and, in other cases, the bridges are ruptured, which result in the appearance of cells with tailed nuclei.

Small alpha-RNP of K-562 cells contain a small RNA as an RNA component, this RNA is homologous to Alu-repeating sequences of human DNA. When cells are exposed to dimethylsulfoxide, an agent inducing cell differentiation along the erythroid pathway, the content of both high-molecular-weight (heterogeneous nuclear and messenger) RNA enriched with Alu repeats and low-molecular-weight specific RNA, small Alu-homologous alpha-RNA undergoes a coordinated decrease. Using the technique of northern blot hybridization, we have demonstrated nonuniform distribution of Alu repeats both in the fraction of total low-molecular-weight RNA of the cytoplasm as well as in the fraction of messenger RNA. It is proposed that alpha-RNA (alpha-RNP) participates in the control of expression of non-linked Alu-containing genes.

Some molecular genetic and biochemical features of malignant breast tumors were studied in females living in North-Western Russia. ERBB-2 oncogene amplification frequently (25%) occurred and was associated with poor outcomes. The frequency of C-MYC extra copies was lower (3%) than that in Europe and the USA. Deletions at chromosome 17p were associated with ERBB-2 amplification and the lack of nodal involvement. Moreover, it is concluded that endogenous hormonal and metabolic parameters, as well their changes due to some environmental factors (smoking), plays a great role in the modification both of breast cancer risk and autocrine-paracrine relationships in the very tumor tissue and of the hormone sensitivity of the latter.

104 surgery cases of non-small cell (NSLC) and small cell lung carcinoma (SLC) are studied. Oncoprotein bcl-2 is found in 49 out of 104 (47%) cases, more frequently in SLC (71%) than in NSLC (44%) and this correlated with carcinoma morphological malignancy. L-myc oncoprotein and EGFR were expressed practically in all cases, oncoprotein of the p53 mutated gene in 57% cases. The highest content of p53 was in SLC, large cell and poorly differentiated squamous cell carcinoma. Percentage of cells with mutated p53 statistically correlated with morphological malignancy of lung carcinoma. Oncoprotein of Rb gene was revealed in 51%, most frequently in squamous cell carcinoma (71%) and particularly in its well differentiated types. IGFII was found in 74% NSLC and in 100% SLC with cytoplasmic location in tumor cells; the level of expression was higher in SLC. IGFII 2 and 5 were more frequently observed in the foci of keratinization of squamous cell carcinoma. For the first time IGFP B3 was found not only in the cytoplasm but in the nuclei of tumor cells as well. There was a significant positive correlation between the content of IGFIBP3 in the nuclei of tumor cells and morphological malignancy (poor tumor cell differentiation, larger size and metastases). The mean number of proliferating Ki-67 positive cells was 24% but this figure was much higher (47%) in SLC. Squamous cell carcinoma is characterized by a more frequent and stronger expression of CD44 types 5 and 6 in the cytolemma and this may be considered as a marker of squamous cell differentiation of lung carcinoma.

Surgery material from 28 cases was studied. Thyroid adenoma differs from thyroid carcinoma by a lower level of expression of Ki-67 and bcl-2, while the mutated p53 expression is lacking. These indices may be used for early and differential diagnosis of thyroid carcinoma. Medullary carcinoma is a tumor with the highest malignant potential and p53 and bcl-2 may serve as markers of a higher degree of malignancy. Ki-67 may serve a marker of proliferative activity of tumors belonging to the same histological type. Thus, its high expression in follicular carcinoma is an index of a high proliferative activity of its cells, correlates with its rapid growth and should be taken into consideration in therapy and prognosis. Expression of bcl-2 clearly correlates with neuroendocrine differentiation of carcinoma and its highest expression was found in the medullary carcinoma as well as in the chromogranin positive cells of the papillary thyroid carcinoma. APUD amyloid deposits in medullary carcinoma and high levels of c-myc in adenomas indicate some genetic restructurizations in malignant and benign thyroid tumors.

The paper presents the results of study on polymorfisms of xenobiotic biotransformation enzymes (CYP1A1, glutathione S-transferase MI and N-acetyltransferase 2) and p53 tumor suppressor protein in patients with lung, stomach and intestine cancer. The frequency of CYP1A1-Val allele in all studied cancer groups was 3 to 5 times higher than in healthy control group. The carriers of homozygous glutathione S-transferase M1 gene deletion and slow acetylator phenotype were also of higher lung cancer risk. The substantial increase in slow acetylator phenotype frequency was shown also in the group of intestine cancer patients. The p53 Arg/Pro polymorphism study revealed the elevated frequency of Arg allele in lung and stomach cancer groups. The risk of lung cancer for the carriers of susceptible alleles depended on the age and smoking status of the patients. The results testify to a high possibility of studied polymorphic genes to be the markers of susceptibility to oncopathologies.