Twin pairs with one or two myasthenic patients were selected from patients with neuromuscular pathology. 18 couples of twins were included in final selection (9 monozygotic and 9 dizygotic pairs). 4 pairs of monozygotic twins were concordant to myasthenia (MA). All dizygotic pairs were discordant to this disease. Matched concordance of monozygotic twins was 44%. Penetration of pathological gene was 61% assuming the hypothesis about monogenic heredity of MA. The coefficient of heredity was 44%. The conclusion was made about important, but not absolute role of hereditary factors in development of MA. It was necessary the presence of combination of both genetic and environmental factors for MA development.

A biomonitoring system is proposed, which involves measurement of environmental genetoxicants, determination of mutagenic accumulation in biological substrates of human beings and the severity of genetic abnormalities in their somatic cells. The toxicogenetical monitoring system includes the assessment of the examinees mental status. The results of application of the system are given by using as an example two Yaroslavl (machine-building and oil-processing) plants.

Our study of B1-associated DNA fragment polymorphism in murine hepatocytes by means of polymerase chain reaction (PCR) allowed to reveal as many as 20 DNA fragments differing in their molecular masses (m. m.) and amount of amplified products varying within the range of 100-1000 bp. Within the same inbred strain of mice (C57B1/6), spectra of B1-associated DNA fragments were similar in different periods of ontogenesis (embryos of 15 and 20 days, adult mice), in different mice of the same or different litters. A comparative analysis of the spectra of B1-associated DNA fragments from hepatocytes of two inbred strains, C57B1/6 and C3HA, has shown in general their similarities in m. m. values. But a significant distinction, that was found, involved the presence of DNA fragments with m.m. approximately 600 bp in the spectra of B1-associated DNA fragments from C3HA strain mice, that is absent in the spectra of respective fragments from hepatocytes of C57B1/6 strain mice. The spectra of B1-associated DNA fragments from transformed hepatocytes of murine hepatoma MH-22a, in general, were the same as those from hepatocytes of C3HA strain mice. At the same time, a DNA fragment with m.m. of 450 bp, not detected in normal hepatocytes, was revealed in transformed ones. Nevertheless a DNA fragment with m.m. of 600 bp, characteristic of normal hepatocytes, was not observed in the transformed hepatocytes. The B1-PCR method can be used for studying genomic polymorphism both in different populations of mice, and during malignant growth.

An immunogenetic examination of 86 cases of stomach cancer established a correlation between predisposition and resistance, on the one hand, and the distribution of allele sets of HLA-genes (classes I and II), on the other. The relationship was found to vary according to sex and age. The most significant relationships with respect to predisposition were identified for HLA-B51 (RR = 19.82) alleles and allele combinations of HLA-DRI-DR7 (RR = 25.52) and HLA-A9-DRI (RR = 33.67). High relative risk of stomach cancer was attributed to the absence of relevant alleles in 91 patients included into the group of comparison. Also, combinations of allele sets were identified in healthy subjects which never occur in stomach cancer patients. The results provide a substantiation for developing an automated system of interpreting HLA-typing data which are instrumental in evaluating the patient's predisposition, resistance and prognosis.

Flow-cytometric assay of DNA levels and proliferative activity of cell in 43 cancers of the breast was carried out. The cytometric data were evaluated versus age, histological malignancy and regional metastasis incidence. The study pointed to a direct correlation between malignancy and aneuploidy (increased fraction of cells featuring unbalanced levels of DNA as well as enhanced DNA index) involved in invasive ductal carcinoma. Aneuploidy and proliferative activity frequency is relatively higher in cases of regionally disseminated tumors. Aneuploidy tumor incidence is higher in age groups under 50 than in older patients.

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was observed in the patients with highly differentiated cell lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII digestion) was observed in the patients with adenocarcinomas as well as in the patients with metastases and low levels of tumor tissue differentiation. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers mentioned above but was associated with type of tumor progression. Previously, it was reported that the mini-satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our data indirectly confirm the hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.

The character of distribution of BoLA class-I antigens was studied in Black Pied cattle populations differing in status in relation to leukemia. Associative relationships of distinct antigens with resistance and susceptibility to leukemia were revealed. Using the statusmetria method, an integral estimate of predisposition to leukemia (Z) was calculated taking into consideration the contribution of each antigen in the immunogenetic status of the animal. The interval of Z values was determined, which allowed animals to be divided into groups according to resistance or susceptibility to leukemia. Alleles of the BoLA-DRB3 gene were typed in subsamples of animals with leukemia and healthy animals by the PCR-RFLP method. Twenty alleles of the gene were detected, and their frequencies were determined in both subsamples. Alleles mediating resistance of animals to leukemia (BoLA-DRB3.2*11, *23, and *28) were distributed in the group of healthy animals with frequencies of 0.079, 0.132, and 0.053, respectively; they were completely absent in animals with leukemia. The data on the estimate of animal status in relation to leukemia, which were obtained by the method of statusmetria taking in consideration the real contribution of the each class-I antigen in the detection of the disease risk (value Z), and data of allele typing by the PCR-RFLP method were shown to be in good agreement. The possibility of using BoLA class-I antigen typing in herds to determine the number of animals with leukemia was demonstrated.

Analysis of literature indicates that genetic mechanisms of thyroid tumor development are connected with two main classes of genes: oncogenes whose activation may stimulate tumor growth and anti-oncogenes which acquire oncogenic properties due to the loss of their function through point mutation or deletion. Protooncogene Ras mutation plays a role in the early events in tumor development. Restructuration of Ret and Trk oncogenes, overexpression of Met and Ras point mutations are characteristic for papillary thyroid carcinoma.

The survey dedicated to the 70th anniversary of the Prof. N. N. Petrov Research Institute of Oncology, St. Petersburg, gives a basic idea of molecular pathogenesis of tumor in humans, particular emphasis being placed on the clinical and applied aspects of molecular oncology. The survey is intended for a wide audience including doctors, professors and undergraduate students majoring in medicine and biology.

A significant role of chemical, physical and hormonal factors modifying transplacental carcinogenesis has been established. It was found that, in tumors induced during gestation by carcinogenic agent treatment, ras oncogenes are activated due to their point mutation. The progeny of male animals exposed to radiation before mating with intact females prove to be more susceptible to such carcinogenic promoters as urethane and TPA than controls while the descendants of older males and young females are more susceptible to NMU treatment than those of young males and females. Convincing evidence of selective DNA damage being relevant to initiation of carcinogenesis was first obtained in experiments involving the use of a synthetic analog of thymidine 5-bromodesoxyuridine. Experimental treatment with carcinogenic agents and tumor promoters at different age has demonstrated age-related accumulation in different tissues of cells which have been randomly exposed to carcinogenic substances and, as a result, are pass at least one stage before complete malignant transformation. It is also assumed that such partially transformed cells are exposed to the carcinogenic effect which increases in proportion to age. Significant differences in age-related changes in the sensitivity of different tissues to the action of different carcinogens have been identified. A direct correlation between the pattern of aging delay in a population affected by a certain geroprotector and its influence on neoplasm development was established on the basis of an evaluation of the evidence on tumor incidence in experimental animals following geroprotector administration.

Our laboratory morphogenetic studies have shown that most esophageal and intestinal tumors arise de novo, i.e. they are not necessarily preceded by the so-called "precancerous lesions". This is particularly true in the case of soft-tissue sarcoma (malignant fibrous histiocytoma and malignant hemangioendothelioma) which never involve "presarcoma" development. However, those investigations provided morphological characteristics of such early preinvasive cancers as carcinoma in situ and superficial cancer. Histological studies showed malignant fibrous histiocytoma to be low-differentiated sarcoma of fibroblastic origin. Wide-range morphogenetic potentialities of derivatives of the neural crest (miogenic differentiation) and Muller's epithelium (manifestation of connective-tissue properties) during tumor growth were identified in the course of the histogenetic examination of Triton experimental tumor and electron microscopy investigation of endometrial and ovarian tumor cells cultured in soft agar.

p53 oncoprotein was studied in 80 astrocytic gliomas of the hemispheres and nuclear expression of this oncoprotein was found in 90% of the tumors this indicating high specificity of the reaction. A tendency to growing oncoprotein expression was found at different stages of malignant transformation showing feasibility of clonal expansion of cells with gene p53 mutation. High variability of the oncoprotein p53 immunoreactivity is characteristic of glioblastomas this suggesting genotypic polymorphism of gliomas of high grade malignancy. The lowest expression of the p53 oncoprotein was in gliosarcomas suggesting mechanism other than mutation. A stable link between the p53 oncoprotein expression and the proliferating cells nuclei antigen was not observed. This finding confirms an independent character of various progression features of the tumor.

Cultured HEp-2 cells (human larynx cancer cells) reveal significant variation in chromosome aberration rate. The study of its regularities at cell and population levels allowed to conclude that the cancer cells contain hidden lesions of genetic structures which, with certain probability, can reveal themselves as chromosome aberrations. Exposure of cancer cells to non-mutagenic agents (suboptimal temperature, low concentration of propilgallate or caffeine) resulted in the increase of frequency of cells containing chromosome aberrations above the control level, while the number of aberration per aberrant cell was not altered. Exposure of irradiated cells to the same agents induced, as in the case of spontaneous mutagenesis, the increase of the aberrant cell frequency, while the extent of their damage remained at the level characteristic of the effect of irradiation solely. The similarity of mechanisms for realisation of hidden chromosome lesions under the action of non-mutagenic agents in spontaneous and radiation-induced mutagenesis indicates the similarity of the nature of these lesions. The convincing evidence of existence of hidden genetic lesions in cancer cells was obtained in experiments with cloning of the initial population and analysis of chromosome aberrations in 22 clones. All the cells without any exception contained chromosome aberrations.

Considerable decrease of expression of some "brain-specific" genes obtained in previous experiments was detected by means of differential hybridization of gridded human fetal brain cDNA library with total cDNA probes, synthetized on mRNAs isolated from the normal brain cells and several tumor cells. In contrast, for few genes expressed on low level in human fetal brain the evident increase of expression level in human brain tumour cells was found. The nucleotide sequences of some of these genes and previously isolated genes which have different specificity of expression were determined.

The analysis of oncoepidemiological state of ovarian cancer (OC) in Kharkov region in comparison with Ukraine within the periods before and after the Chernobyl NPP accident was conducted. Territorial differentiation of this pathology in the regions of Ukraine are represented. An increase in OC incidence among the women of Ukraine and Kharkov region was detected, especially increase of OC the south-east regions. Clinical genealogic analysis in the families of 102 probands with OC, 60 women with benign ovarian cystomas and in 258 practically healthy women revealed malignant tumors of different locations. In probands with OC, the accumulation of this tumor, breast cancer and cancer of gastrointestinal tract was found. The necessity of clinical genealogic analysis of Ukrainian women was based.

The equation for the increase of tumor frequency with age is deduced from the supposition about the errors of DNA replication as the main cause of oncogenic mutations. The quantitative expression of the organ specificity of tumor frequency is concluded also. The age function coincide qualitative with epidemiologic date: the tumor frequency is in proportion to age with the exponents of 5 and higher. The frequency of oncogenic mutations on one DNA replication is evaluated from the equation using the statistical data of the annual sickness rate of the lip, oral cavity and throat cancer for the men and the rate of cell proliferation in this organs.