A cytogenetic observation, that the sister chromatid exchanges (SCE) occur 3 times more frequently in a special form of xeroderma pigmentosum--XPII than in the norm, prompted a study of DNA replication in this rare disease. Using DNA fiber autoradiography, the rate of fork movement and the frequency of initiation in the adjacent clusters of replicons were estimated. The rate of fork movement was significantly slower than that in classical XP and in normal cells. Here evidence was provided on another defect in DNA replication in XPII that involves a significantly decreased number of simultaneously operating adjacent clusters of replicons, which results in a decreased rate of DNA chain-growth. According to the Painter replication model for SCE, the exchanges arise due to double-strand DNA breaks occurring on the border between two adjacent clusters, respectively, completely and partially replicated. A retarded fork-displacement rate together with a decreased rate of DNA-chain growth may cause this situation to persist longer than in the norm. Thus, our data provide a further support of the replication model for SCE. A similar combination of cytogenetic and molecular defects has been obtained earlier in the Bloom syndrome cells.

The argyrophilic staining of nucleolar organizer regions (AgNOR) has been found to be of increasing use in routine and experimental histopathology in the study of certain neoplastic lesions. The AgNOR reaction demonstrates the presence of argyrophilic non-histone proteins within NORs. The number of detectable NORs depends on several factors: the level of transcriptional activity, the number of NOR-bearing chromosomes in the karyotype, and the stage of the cell cycle in which they are sought. In man, five chromosomes have NORs, and these areas are the sites which hybridize with rRNA and are of importance with respect to the ultimate synthesis of protein. The results of AgNORs might be more informative if this technique would be applied simultaneously in cytological and histological specimens for each patient. It may also be important to examine the AgNORs profiles in stromal cells.

A clinico-genealogic investigation was carried out in 216 patients with endometrial cancer. Familial accumulation of endometrial and other cancer incidence was established. The segregation rates appeared to be lower than those expected from simple Mendelian models (2-11%). A multifactorial nature of endometrial cancer in overall susceptibility to the disease was found to be at 61%. A genetic correlation analysis showed endometrial cancer to share common genes with breast and gastric cancer in females. Tables of recurrent risk of the disease for relatives were prepared to be used in medico-genetic counseling.

Risk factors of bladder cancer development were studied in a population-based case-control epidemiological study performed in Moscow. Relative risk (RR) indexes appeared to be increased in smokers (4.2) and ex-smokers (3.5) with statistically significant trends for two most important factors such as duration of smoking and duration of withdrawal. A pronounced although insignificant increase in the RR indexes was established for drivers (3.0) and a slight insignificant rise-for gas arc welding operators (1.5). The indexes were increased in subjects with a family history of cancer. The relative risk of cancer was significantly lower in beta-carotene consumers. A preventive effect of polyunsaturated fatty acids and oil and margarine used for frying was established. Risk of bladder cancer tended to increase with a rise in dietary protein. A dose-effect type inhibition of advancement of the disease by vitamin C was observed.

beta-Casein genes expression in breast epithelium was studied in male patients with various forms of gynecomastia and cancer. Blood serum levels of pituitary, sex and glucocorticoid hormones were assayed in 29 patients with gynecomastia and 22 cases of breast cancer, and in 25 of them beta-casein genes expression was evaluated additionally. Activation of the above genes was established in the tissues studied. Their level proved to be in a correlation with that of prolactin.

The occurrence of ERBB-2 (HER-2/NEU) oncogene amplification was studied in 203 DNA samples obtained from 175 cancer patients. Amplification of ERBB-2 oncogene was established in 14 out of 63 (22%) patients with breast cancer, 1 out of 23 cases of ovarian tumor, 1 out of 19 cases of large bowel cancer and 1 out of 27 patients with cancer of the thyroid. Patients with lung cancer (34), soft tissue sarcoma (6) and malignant melanoma (3) failed to reveal any changes in the above oncogene. A tendency was established for ERBB-2 oncogene amplification to be associated with lymph node involvement in female patients with breast cancer: amplification was observed in 9 out of 28 patients presenting with lymph node metastases and only in 5 out of 29 metastases-free cases. To summarize, ERBB-2 oncogene is fairly often activated in human tumors but a high occurrence of the gene amplification was observed in female patients with breast cancer only.

An analysis was carried out of chromosomal site-fragility in patients with primary multiple tumors and familial breast cancer. A possible correlation is discussed between fragile sites, breakpoints in chromosome rearrangements in cancer patients and the localization of oncogenes mapped in chromosomal regions involved in said rearrangements.

Without having the common high specific marker, the tumours of the nervous system are, however, characterized by regular quantitative and structural changes of chromosomes. In this review molecular and genetic aspects of chromosome translocations typical for the main types of the nervous system, their role in activation of protooncogenes and their conversion to oncogenes, which is able to cause tumor transformation, are considered. Additionally, the role of chromosome translocation in the inactivation of suppressor genes is discussed.

Expression of myc, fos, src, ras and sis oncoproteins was studied in biopsy material of tumors, metastases and "normal" surrounding tissues from patients with different histological types of stomach and lung cancer, melanoma and other malignancy using immunoblotting. Besides, the immunohistochemical distribution of these oncoproteins under lung cancer and precancer conditions was analysed. The oncoproteins expression was significantly higher in cancer as compared with precancer and "normal' surrounding tissues. C-myc and c-fos gene products were detected in all the malignant tissues irrespectively to histogenesis of tumors, while the level of c-myc expression was rather high. The high level of c-fos expression was observed in stomach carcinomas and at early stages of lung tumor progression. C-src and c-sis genes expression varied in tumors of different histogenesis. C-src proteins were found in 60% of lung cancer but it was practically absent in stomach carcinomas and in melanomas. C-sis gene product was observed in some melanomas and lung carcinomas. Ras gene can be activated at early stages of tumor progression of stomach carcinomas and lung adenocarcinomas and at later stages of tumor progression in melanomas and small-cell lung carcinomas. Thus, there are some correlations between oncoprotein expression and tumor tissue histogenesis and progression.

DNA isolated from lung and liver tumor which were induced in CD-1 mice by transplacental treatment with 7,12-dimethylbenz(a)anthracene (DMBA) or developed spontaneously was analyzed for the presence of Ha- and Ki-ras oncogene codon 61 mutations. The A to T transversions at the second position of Ha-ras codon 61 were revealed only in liver tumors of DMBA-exposed animals, whereas only Ki-ras mutations occurred in both spontaneous and induced tumors of the lung. A to T mutations at the second position of Ki-ras codon 61 or non-identified yet mutations at the third position of the same codon were shown to be related to DMBA treatment. Thus both tissue and carcinogen specificity of ras oncogene activation was clearly demonstrated.

Expression of protooncogenes c-myc, N-myc, c-fos, Ha-ras 1, Ki-ras 2, yes, abl, src, N-ras, met and mos was studied in human gastric tumors and in rat gastric mucosal membrane during gastric carcinogenesis induced in rats by means of N-methyl-N'-nitro-N-nitroso guanidine (MNNG). Elevated expression of protooncogenes c-myc, c-fos, Ha-ras 1, Ki-ras 2, N-myc and Raf 1 was observed in carcinomas of human stomach. Amplification of Ha-ras 1 protooncogene was found in the human gastric tumor and metastasis. Point mutation was not detected in 12 the codon of Ha-ras I protooncogene. Expression of these protooncogenes was not altered during gastric carcinogenesis induced by MNNG in rats. However, within early steps of cancerogenesis (9 days, 3 months) amplification of ribosomal genes occurred in rat gastric mucosal membrane and in adenocarcinoma developed, while the tumor growth was accompanied by activation of mitochondrial genes.

Effect of alpha-melanocyte stimulating hormone (MSH) on proliferating activity of MS and BRO melanoma cell strains with dissimilar phenotype was studied. MSH, apart from the effect on melanomagenesis, influenced the cell proliferation. Growth of MS cells was inhibited at 10(-8)-10(-9) M concentrations of the hormone (IC50 = 2.10(-8) M), while BRO cells were activated. The higher concentrations of MSH inhibited also BRO cells growth (IC50 = 9.10(-7) M). Ligand-receptor interaction of 125I = MSH with plasmatic membranes and cytosol fraction of the cells was studied at 4 degrees and 37 degrees.

This is a brief review of different ideas on the mechanism of cell malignization united by the mitochondrial conception of carcinogenesis. According to this conception, primary trigger factors of carcinogenesis (free radicals, carcinogens, heat fluctuations) induce damage to mitochondrial DNA and membranes that results in the rearrangement of cell energy metabolism to glycolytic type and disturbance of mitochondrial structure and reproduction. The injured part of mitochondrial DNA incorporating into nuclear DNA induces activation of oncogenes, appearance of oncoproteins and malignization of cells.

Length polymorphism of restriction fragments of oncogene HRASI was studied in 52 patients with lung cancer as compared with corresponding normal tissues and leukocytes of these patients and of healthy volunteers. Enhanced frequency of one of main alleles of HRASI A4 was found to correlate with development of the disease aggressive symptoms. Alterations in the HRASI locus of tumoral DNA appear to correlate distinctly with the elevate frequency of the allele (P less than 0.01). Relationship between the allele A4 and active metastases spreading in lung cancer of the III-IV stages as well as specific rearrangements as a result of which allele A4 maintained unaltered or even amplified in carcinomas enabled to suggest that the allele A4 of HRASI oncogene serves as an endogenous risk factor in impairment with non-small cellular lung cancer in addition to typical exogenous factors such as smoking.

A human interleukin-2 (IL-2) gene was isolated from genomic DNA library. The isolated gene with 5'- and 3'-flanking sequences of various lengths was inserted into plasmids derived from the retroviral vector pPSneo. The recombinant plasmids were transfected into myeloma X63Ag8-653 cells. The transfected cells, harbouring the IL-2 gene with the shortened (to position -165) or totally deleted 5'-flanking sequence, constitutively expressed biologically active IL-2. Deletion of 3'-flanking region on did not affect the IL-2 expression.

A retrospective analysis of the case histories of patients with familial and nonfamilial ovarian carcinomas has shown that patients with the familial condition develop a higher resistance of the body to tumor dissemination and their survival rate is better. This conclusion may be of interest for those who research carcinogenesis mechanisms.

By the restriction analysis method we established that methylation of the 5'-end cytosine in 5'-m5CC-3' duplexes had individual specific features. This genetic peculiarity did not change even in DNA from human stomach carcinomas.