Clincocytological features of leukemia were investigated in 58 infants of the first year of life. Among these infants the sucklings present the most unfavourable group with respect to the disease prognosis. Specific clinical symptoms were most manifest in patients with congenital acute leukemia (21), and congenital chronic myeloid leukemia (20 patients). Cytogenetic investigation has revealed anomalic karyotypes (some of them are similar) in most of infants with congenital acute leukemia. In three patients with congenital chronic myeloid leukemia a typical Philadelphia chromosome has been detected, that is a rather rare case.

Cytogenetic and mitotic disorders were studied in 151 patients with acute non-lymphoblastic leukemia. A significant rise in the incidence of clonal disorders with predominant affection of chromosomes 5 and 7, and an increase in the percentage of cases with the presence of pathologic mitoses in hemopoietic cells have been recorded in patients who, due to their occupation, have been exposed to potentially mutagenic chemical substances.

Among patients with Hodgkin's disease 30 cases of the family disease were revealed during 1972-1988. The occurrence of family pairs of patients with Hodgkin's disease suggests a heritable anomaly or inheritance of a gene predisposing for this disease. In cases of contacts with second degree relatives and children from a single family, one cannot exclude a role of environmental factors and a concurrent transfer of the infectious factor. However, cases of family Hodgkin's disease might be due to a pure coincidence.

Operative material obtained from patients with lung cancer and precancer, carcinoids, secondary tuberculosis, chronic nonspecific diseases and pulmonary lymphosarcoma was examined immunohistochemically. Expression of the oncogenes was higher in lung carcinoma than in the foci of lung epithelium regeneration, metaplasia and dysplasia. All the oncogenes in precancer and cancer may be divided into two groups by the degree of their expression: oncogenes the activation of which occurs in the same way at certain stages of tumour progression regardless of the lung carcinoma histogenesis and oncogenes expressed at certain stages depending upon the carcinoma histogenesis. The majority of oncogenes studied may be included into the second group (C-myc, ras, sis, src) and only one c-fos into the first group. The oncogenes expression may occur at the precancerous stage and precede the morphological changes in cells and tissues. The expression of some oncogenes (C-myc, sis) takes place not only in the tumour parenchyma but in the cancer stroma as well thus making the immunohistochemical method most reliable that permits one to study a true expression of oncogenes by cancer cells.

Current concepts on oncogenes, "antioncogenes" and their role in tumorigenesis are presented. Normal functions of proto-oncogenes, mechanisms of their conversion to oncogenes and inactivation of "antioncogenes", effects of oncogenes in model systems in vitro and in vivo are considered. Special attention is paid to the nonrandom proto-oncogene and "antioncogene" alterations in human tumours and the possibilities of their use as diagnostic or prognostic criteria.

The pathogenetic and clinical significance of karyotype features in leukemia and preleukemia are analysed. In 34.7 per cent patients with preleukemia, karyotype instability was observed which consisted in numerical and structural chromosome aberrations with clone anomaly. It was found that karyotype instability is an initial stage of anomalous clone formation and often precedes its development in preleukemia, secondary leukemias, and in preblastic stage of chronic myeloid leukemia. Acute leukemias were found to be characterized by premeditated numerical and structural chromosomal aberrations with predominant involvement of chromosomes 5, 7, 8, and 21 in non-lymphoblastic and chromosomes 6, 9, 8, and 21 in lymphoblastic forms of acute leukemia. It was also shown that the normal to abnormal metaphase ratio in acute leukemia patients is of high prognostic value.

The biological features specific to the tumor growth in acute leukemia are responsible for the disease prognosis and its response to polychemotherapy. Current molecular-biological, karyological, cytological, kinetic, and culture investigation techniques have contributed much to the understanding of the pathogenesis of acute leukemia and may be used as a guide to appropriate disease management.

One hundred and ten families having one child suffering from acute leukemia were included in HLA studies. These families were found to have unequal distribution of the parent HLA-haplotypes among the sibs. Three groups of families were conditionally distinguished. The first group showed the predominance of one parental, the second group of one maternal, and the third group of one maternal and one paternal HLA haplotypes. This suggests that impairment of the evolutionally derived principle of equal participation of both gamete types of each parent in the zygote formation is deleterious for the progeny.

Fourteen cases of the ovarian carcinoma (OC) were studied for alterations of c-myc and c-Ha-ras-1 oncogens. Amplification of c-myc was found in four aggressive and widespread OC. An increased frequency of one of the four common alleles of c-Ha-ras-1-allele A4-was determined in OC patients. Rearrangements of c-Ha-ras-1-allelic deletions and change in the allele fragment length-were found in all OC with A4 allele. In contrast, no alterations were detected in tumours without allele A4. Thus allele A4 of c-Ha-ras-1 may be viewed as a genetic marker of predisposition to OC in combination with other clinical parameters. Alterations of c-myc and c-Ha-ras-1 oncogens were observed in 8 out of 14 OC samples suggesting that the development of this type of human neoplasm is due to rearrangements of these genes.

Chromosomal damages and their dynamics in blood lymphocytes of mongrel white L10 rats treated (once) intravenously with nitrosomethyl urea (NMU) at a dose of 50 mg/kg have been analyzed. A direct correlation is revealed between carcinogenesis, chromosome aberration level in somatic cells, polyploid and hyperaneuploid cell frequency 24 hs after the NMU treatment and in the precancerous period. An increase of hyperaneuploid and polyploid cells in the organism can serve as a prognostic factor of carcinogenesis.

In the past years the authors advanced a hypothesis of the "age-associated layers" of parent hemopoietic cells. The hypothesis was based first of all on the differences in the patterns of leukemias and noncancerous diseases (of the hemopoietic tissues) in children and adults. The nature of the changing age-associated characteristics of parent cells remained obscure. Analysis of leukemias and epithelial tumors of radiation nature, formed in the victims to nuclear bomb explosion in Japan in 1945, analysis of leukemias occurring in persons with genetic diseases characterized by the known chromosomal aberrations (Down's syndrome, Louis-Bar syndrome, etc.), studies into the inherited forms of leukemias (chronic lympholeukemia, subleukemic myelosis, etc.--all these conditions are marked by the unstable genetic apparatus and high mutability) allowed the authors to make a conclusion about a kit of active differentiation genes which are replaced in health with age. Cancerous transformation may take place just at the level of those genes in parent cells with an unstable genome, since there appear specific mutation (in contrast to nonspecific ones characterizing the unstable genome) and a cancerous clone.

As a result of clinico-genealogical analysis of data on 691 skin melanoma patients, a classification of skin melanoma was elaborated which reflected the etiologic heterogeneity of the disease. Inheritable and non-inheritable forms of skin melanoma were identified. The inheritable tumor group included familial disease (2%) and tumors developing against the background of hereditary diseases and syndromes (32.7%). The data obtained served as basis for the identification of families with high genetic predisposition to skin melanoma development and for the assessment of individual risk of the disease in patients' relatives.

A model describing the mechanism of linear integration of cellular and viral DNA is proposed. The possible role of cellular DNA integration in the process of human carcinogenesis is considered.

The results obtained provide evidence concerning the nature of the Hodgkin and Reed-Sternberg cells. The data based on application of new methods developed during last years such as different enzymo- and immunocytochemical techniques, monoclonal antibody and lectin application and molecular studies of gene rearrangement are presented.

A method of the restriction analysis by Msp I enzyme has been used to analyze the 12th codon of Ha-ras-1 protooncogene in 10 human carcinomas and in the stomach mucosa adjacent to them their 5 metastases into the regional lymph nodes and in 2 ulcers. No point mutation was found.

Results of investigations on the role of protooncogenes in the regulation of proliferation and differentiation of normal hemopoietic cells and in the pathogenesis of tumoral hemopoietic diseases are reviewed. The ways of the protooncogene activation in leukemias are discussed.