The recent data on cellular oncogenes and their significance in the origin of leukemias and lymphomas are reviewed. A brief historical note of the discovery of cellular oncogenes on the example of the Rous sarcoma virus and its cellular homologue is presented. The connection between chromosome translocations and oncogene activation as well as implication of carcinogens and genetic factors is elucidated. The proteins encoded by cellular oncogenes are described and possible pathways of their transforming activity are analyzed.

The activity of LDH M- and H-forms, nuclear DNA contents and of genome mutation rates in the Ehrlich ascitic carcinoma cells were studied after transplantation to the intraperitoneal cavity, subcutaneous connective tissue (SCT) and the eye anterior chamber (EAC). SCT and EAC cultivations demonstrate the increase of M- to H-forms activity ratio due to a lesser H-form activity; so, LDH profiles appear to be associated with such a spontaneously highly differentiated adenocarcinoma of murine breast cancer. SCT and EAC cultivation leads also to changes in the karyotypic structure of cell population--there are no polyploid cells (DNA content is more than 4c). It may result from a sharp fall in genome mutation rates in the Ehrlich ascitic carcinoma clones following EAC proliferation which appears 47 times lower than those during lung proliferation. The data obtained favor a hypothesis that the increase in differentiation level and decrease in tumorigenety of cancer cells during EAC proliferation may be due to selection of the near-diploid cells and to the reduction in genome mutation rates, which in the whole results in decreasing genotypic and epigenotypic variability in tumor cell populations.

The effect of parental age on mutation rates of achondroplasia, neurophibromatosis, hereditary gastrointestinal adenomatosis and Duchenne muscular dystrophy loci was studied. A significant parental age effect on the occurrence of new mutations for achondroplasia and neurophybromatosis was shown. The paternal component of this parental age effect was the major factor in the occurrence of such mutations. The risk of the occurrence of new cases of achondroplasia and neurophybromatosis, as compared with their overall frequency, due to new mutations, are increased by a factor of 2 and 3, respectively, up to the paternal age of 50. The possibility of application of the data obtained in genetic counselling is discussed.

Recent data on cell oncogenes, recessive mutations of certain genes which result in malignization, protective effects of polyploidy are discussed from the standpoint of mutation hypothesis of carcinogenesis. In general, these data and models confirm main conclusions of the two-step hypothesis of carcinogenesis which was put forward by V. A. Strunnikov in 1958.

Tumor Djungarian hamster cells resistant to 5-bromodeoxyuridine (5-BrdU) were inoculated to newborn hamsters. Tumors occurred in animals and were seeded into HAT medium in vitro. This procedure permitted to select hybrids between tumor and normal cells established in vivo. Hybrid nature of cell cultures was confirmed by karyological analysis. Hybrid cells were tested for their ability to grow progressively in newborn Djungarian hamsters and to form colonies in soft agar. The hybrid cells were less malignant than 5-BrdU-resistant tumor cells, but they could grow in soft agar with the efficiency of the parental tumor cells. Chromosomal constitution of the hybrid tumors indicate that as a rule, the expression of malignancy correlates with elimination of the morphologically normal chromosome pairs No 1, 4, 6, 8. Our data suggest that at least two genes located on different chromosomes of the normal cell are needed for suppression of malignancy in somatic cell hybrids.

A hypothesis is proposed on the role in the radiation carcinogenesis of mutation and (or) activation of combination of the several prooncogenes, some of which are homologous on the growth factors or probably to the actin. The antibodies to the products of oncogenes may be used to study mechanisms of carcinogenic action of radiation and others factors or even as diagnostic tool or remedy.

The frequency of several kinds of cancer among relatives of 200 patients with ovarian cancer was analysed. The annual population incidence was used as a control. Nonrandom familial clustering of ovarian cancer (p less than 0.01) was observed. The frequency of breast cancer in women and that of eosophagal cancer in man was higher than the expected value (p less than 0.05). The risk of ovarian cancer occurrence amounted 9% in women of the first degree of relationship, whereas cumulative risk in a population only reached 1.57% to the age of 90. The patterns of distribution of patients in the pedigrees satisfied the requirements of the multifactorial model. Heritability coefficient was 54.12 +/- 2.49%. Thus, women of the first degree of relationship compose the high risk group.

The prevalence of hereditary autosomal dominant gastrointestinal adenomatosis in the Moscow population was estimated on the basis of elaboration of an indirect method. This estimate was found to be 1:48000. The prevalence observed is discussed in terms of ascertainment problems and peculiarities of the method of calculation proposed.

A cytogenetic analysis of blood and bone marrow cells of 15 polycythemia vera patients was carried out at different stages of disease during the G-banding technique. Chromosome aberrations of single character were noted before treatment only in one case, i.e. with the patient at stage II of disease. Cell clones with marker chromosomes were revealed in 6 of 9 patients examined in the course of treatment at stages II and III. The cytogenetic analysis was applied to the terminal stage of polycythemia (blast crisis) in one case, when 3 aberrant clones with multiple quantitative and structural chromosome rearrangements were discovered in blood cell cultures with and without PHA. No preferential involvement of definite chromosomes in aberrations was noticed in all the cases examined, no deletion of the 20q --chromosome being discovered. The role of the treatment in the induction of chromosome aberrations is discussed in addition to its dependence on the stage of disease. It is possible that all the clones of pathological character may appear during the long-termed course of polycythemia in patients treated at more serious stages of the disease.

Hemoglobin fractions were studied in 80 patients suffering from nephroblastoma (Wilms' tumor). 10 out of 80 children had an elevated fetal hemoglobin value, higher than 2.5%, but as there was no other evidence for a thalassemia, we could not refer these patients to delta beta-thalassemia heterozygotes. An electrophoretic study of hemolyzates showed that 4 children had a uniform "quickly-proceeding" anomalous hemoglobin fraction localized in front of HbA2 which decreased in time. In one case, this anomaly was discovered in propositus and also in his father and paternal grandmother. A child suffering from unilateral sporadic Wilms' tumor and his mother had a Negro type hereditary persistence of fetal hemoglobin (HPHF). This complex of Wilms' tumor and HPHF is described for the first time. HPHF and nephroblastoma complex as a possible variant of intersticial deletion of the short arm of chromosome 11 is discussed. The diagnostic value of the study of hemoglobin fractions and the activity of enzymes (catalase, LDH-A), whose genes are localized on the short arm of chromosome 11, are also discussed. It would be useful for genetic counselling to select a group of children with high risk for nephroblastoma.