Mutations of the p53 tumor suppressor are often observed in various human malignancies including blast crisis of chronic myelogenous leukaemia (CML). The pattern of p53 mutation in CML shows some peculiarities as compared with the majority of other neoplasias. In particular, the substitutions at codon 273, one of the most common p53 alteration in various tumors, are not characteristic of CML. To test whether distinction in the pattern of p53 mutation are associated with certain peculiarities of biological effects of different mutant proteins in myeloid cells, we obtained and analysed a panel of human K562 cell sublines expressing various exogenous p53: human Pro156, His175, His194, Trp248 and His 273, or murine temperature-sensitive (ts) Val135 that has properties of mutant protein at 37 degrees C, but shows activities of wild-type (wt) p53 at 32 degrees C. We have found that expression of wt-p53 enhanced the dependence of cells on growth/survival factors, incubation of sparse (< 10(5) cells per/ml) K562/Val135 cultures at 32 degrees C caused apoptosis. In media conditioned by cells of different origin (K562, colorectal carcinoma LIM 1215, Rat1 fibroblast) the p53-dependent apoptosis was inhibited. In conditions that do not lead to apoptosis, the expression of ts-wt-p53 was accompanied by dramatic increase in the number of cells containing glycophorin A (GlycPhA) and "antigen of erythroblasts"--specific markers of erythroid differentiation. Unlike the wt-p53, the majority of tumor-derived mutant p53 (Pro156, His175, His194, Trp248) increased cells survival in media with low serum content and decreased the number of cell expressing GlycPhA, CD9, CD15 and CD71 differentiation antigens. On the other hand, expression of His273-p53 caused a significant augmentation in the number of CD9-positive cells and enhanced the dependence on growth/survival factors that are present in serum or conditioned media. The data obtained are consistent with the idea that unusual pattern of p53 mutations in CML can reflect the peculiarities of the effects of some mutant proteins on differentiation and/or viability of leukemic cells.

The BI-PCT method showed the profile of BI-associated fragments of LNA in the cell line of the mouse hepatoma MH-22a to differ from that of the liver cells of C3HA mice, hepatoma cells incorporating the DNA fragments with 450 bp and those with 600bp disappearing. Application of the same method failed to reveal any differences in the profiles of BI-associated DNA fragments in the differentiated and non-differentiated cells of the embryonal carcinoma F9 induced by retinoic acid and cAMP dibutyryl treatment. It is suggested that the spectra of BI-associated DNA fragments might correlate with genetic stability in tumor cells.

Relationships between genetic polymorphisms (ABO, RH, HP, TF, GC, Pi, ACP1, PGM1, GLO1, PTC) and some clinical, biochemical, and functional parameters were studied in patients with epidermoid carcinoma of the lung who were divided into 2 groups: those with uncomplicated and complicated postoperative courses of the disease. They were found to be different in the two groups. The values of ESR, albumin, lymphocytes, vital capacity, and RQ are the most distinctive signs that differentiate the patient groups. A high correlation was found between the signs in patients with an uncomplicated postoperative course. A less correlation between the signs, as a higher intergroup variability in the majority of the signs under study suggests that there is a significantly impaired physiological homeostasis in the group of patients with a complicated course. Comparing the mean values and dispersions shows their equal direction in the two groups of patients irrespective of their genetic polymorphism. The GC system is associated with profound changes of the studied signs in the group of patients with an uncomplicated course and GC*1F carriage should be regarded as a poor factor in the prognosis of the disease.

The yield of UV-induced DNA double-strand breaks was studied for white blood cells ("light" fraction) derived from peripheral blood, and from patients with lymphomas, chronic lymphoid leukemia (CLL), and chronic myeloid leukemia (CML). The method employed was constant-field electrophoresis of plug-embedded DNA in agarose gel. Characteristic dose-response curves were obtained for various cell populations. Lymphoid cells, both from healthy subjects and CLL patients, revealed less damage to DNA under UV-irradiation, whereas CML cells were much more affected. Possible interpretation of these results includes species-specific differences in UV-induced DNA damage, as well as sufficient DNA crosslinking, thus interfering with DNA dsbs detection in irradiated cells.

Non-Hodgkin's malignant lymphoma was diagnosed in 66 patients by immunophenotype technique using a batch of 13 Russian-isolated monoclonal antibodies which help identify antigens of T- and B-lymphocyte surface membranes. Polyclonal light chains of immunoglobulins and T- and B-cell antigens were identified in the course of histological examination of biopsy material sampled from hyperplasia lymphoid tissue. B-cell lymphomas revealed monoclonal light chains of immunoglobulins and positive B-cell antigens. T-cell tumors had mostly T-cell antigens and no light chains of immunoglobulins. Neither common leukocyte antigen, nor panT- or panB-cell antigens were found in 7 cases of cancer metastasis to lymph nodes.

Flow cytometry was employed to assess DNA level and proliferative activity of cells involved in 49 cancers of the large bowel epithelium. Also, 17 samples were taken from subjects without tumor pathology of the gastro-intestinal tract. Fifty-five percent of adenocarcinomas had aneuploidy (63%) in which cases over a half of cells revealed abnormal DNA levels. While aneuploidy was identified in one-third of cancer patients, similar cells were observed in the microscopically-unaltered epithelium at a varying distance from tumor, the intact intestinal epithelium being invariably diploid. The proliferative activity of colonic adenocarcinoma was shown to be significantly higher than that in rectal tumor and intact epithelium.

Complementation groups for xeroderma pigmentosum (XP) and Cockayne's syndrome (CS) cells have been first determined for patients encountered in the former Soviet Union. The determination was carried out using fusion of fibroblasts to be examined with those of already known complementation groups, and subsequently registering the level of DNA unscheduled synthesis (for XP cells) and RNA synthesis recovery (for CS cells) after UV-irradiation. The evidence of the complementation was normalization of these indexes. Cells of XP2SP and XP4SP patients are shown to fall under the XPC complementation group, whereas CS1SP cells are classified within the CSA complementation group.

The report deals with the predictive value of a procedure for lifetime detection of tumor in experimental animals. The database included the results of regular cAMP/cHMP tests carried out in 54 rats with radionuclide-inducted tumors and 24 tumor-free rats. The data were processes by statistical methods and the informative value was determined on the basis of standard recommendations. The test was shown to have high sensitivity (85.2%), sufficient predictive value (73%) and diagnostic effectiveness (68%). Application of the test in groups of humans at high risk of tumor development is discussed.

Amplification of the int-2 oncogene was observed in 10 out of 78 (13%) samples of DNA isolated from cells of primary breast tumor. A clinico-morphological examination established a correlation between this molecular-genetical anomaly and tumor size: gene amplification was detected in 1 out 34 (3%) cases of breast tumor under 2 cm and in 9 out 44 (20%) tumors measuring 2 cm and more (p < 0.05). Similarly, a kind of correlation was found between gene amplification and low differentiation of breast cancer cells: enhanced copying ability of the oncogene was registered in 2 out 4 (50%) breast tumors with low cell differentiation, 8 out 69 (12%) tumors with medium cell differentiation, while it was not identified in 5 breast carcinomas with high cell differentiation (p < 0,2).

To elucidate feasibility of accurate diagnosis of chronic myeloid leukemia (CML) without cytogenetic and molecular-genetic investigations as well as to specify CML diagnostic criteria, clinicohematological parameters were compared in two groups of patients: with Ph'-chromosome and/or rearrangement of fragment bcr (group 1), with unknown karyotype in whom detection of bcr fragment rearrangement was not made. Clinicohematological parameters in both groups were close in absolute value and underwent parallel changes in the course of leukemia progression. In group 1, patients in progressive and blastic phase compared to patients in chronic phase had a 14-fold increase in the number of additional cytogenetic anomalies. In patients with tumor transformation fragment bcr underwent rearrangement according to type B2A2. Thus, the diagnosis of typical CML variants is feasible without detection of Ph'-chromosome and/or rearrangement of bcr fragment. It is especially true and essential for patients in the chronic phase. The data obtained provide more accurate diagnostic criteria of CML.

Bone marrow cellular DNA content was measured by flow cytometry in 107 adult patients with various types of acute leukemia. DNA-aneuploidy was detected in 28 of 107 patients (26%). In 18 patients with DNA-aneuploidy bone marrow was examined throughout 2-36 months. DNA-flow cytometry of bone marrow allows to determine DNA content in leukemia cells and distinguish hypodiploid, diploid, hyperdiploid and tetraploid DNA clones in patients with acute leukemia. In some cases this method allows monitoring of the minimal residual disease.

The paper presents some experimental data and speculations about antituberculous resistance and immunity in mouse mutants resisting spread of transplantable syngeneic tumor.

DNA level and proliferative activity of malignant cells (89), atypical (7), glandular and glandular-cystous hyperplasia (15) of the endometrium and normal endometrium (28) have been assayed by flow cytometry. The results were evaluated versus degree of cell differentiation, depth of invasion and expected clinical prognosis. A reverse relationship was established between aneuplody frequency on the one hand, and cell differentiation degree and poor prognosis, on the other. However, a direct correlation was observed between DNA index and tumor aggressiveness. It was demonstrated that proliferative processes are much more active in non-differentiated cell carcinoma of the endometrium.

A medico-genealogical study was concerned with a line consisting of 38 members. Four of 18 women had breast cancer (BrCr) and one-leukemia. BrCr was diagnosed in the 1st generation in the proband's grandmother (1-2) at the age of 40 and in the 3rd generation: in the proband (III-8) at the age of 43 and in two of her sisters at the age of 44 (III-2) and 48 (III-10), respectively. Breast tumors appeared in the 3rd generation patients approximately at the same age. A cytogenetic study of venous blood lymphocyte metaphases using G-banding of chromosomes revealed homogeneously-stained regions in 100% of cells in the proband's chromosome I: (q11-q12). In the proband's asymptomatic daughter (IV-9), pronounced chromosomal instability (ruptures in chromosomes and chromatids in 50% of cells) was observed. Also, single and multiple double minutes were detected in 10% of cells, while marker 14(p12-pter)-in 100%. This marker was also identified in 100% of lymphocytes taken from the asymptomatic daughter (IV-11) of the proband's sister (III-10). The nature and significance of cytogenetic markers detected in blood lymphocytes of the proband and said siblings are discussed. Heritability of said cytogenetic markers pointing to predisposition to cancer development (of BrCr in said family) is suggested.

The development of radiation osteosarcoma genesis scheme induced by 90Sr was the subject of the present study. The production of cancer cells after exposure to a specific dose-rate of emitting 90Sr incorporated in the skeleton are typical for the initiation period. However not all the cells remain in the mutant DNA. In some of them DNA reparation occurs, other cells are killed in the process of the subsequent divisions, and only a few of them containing mutant DNA are preserved in the state of repression up to the end of life time. Disorders of homeostasis due to exhausted of physiological reserves - (natural or early aging) are manifested as a promoter. In that period the derepression of mutant DNA occurs and malignant growth of tumor starts.

Whether the DNA index (DNAI) of tumor cells and serum carcinoembryonic antigen (CEA) may be used to make prognosis in 78 patients with epidermoid lung cancer at the stage of T1-3 N(o) Mo was studied. There was a direct correlation between tumor ploidy and CEA levels. The two-year relapse- free survival among the operated-on patients at the stage T1-2 N(o) Mo was not shown to be associated with DNAI. At the same time in the T1-3 M1-2 Mo patients radically operated on, the two-year survival correlates with DNAI: it is significantly (p < 0,05) higher in patients with diploid tumors (DNAI = 1.0) than in those with aneuploid cancer (DNAI > 1.05). The patients with low preoperative CEA levels ( < 10 micrograms/l) have a more favourable prognosis after radical surgical treatment.