The effects of 2',5'-oligoadenilates (2,5A) on the survival of Wistar rats inoculated with Svec leukemia cells and the proliferation of tumoral cells were investigated. An agreement between the expression of c-myc protooncogene and inhibition of leukemic cell proliferation by 2,5A was found.

Evidence for the role of dysplastic nevi (DN) in the development of cutaneous malignant melanoma (CMM) is presented. Primary multiple foci of CMM were found considerably more frequently in individuals with DN. The frequency of primary multiple CMM was found to be 3.1% in males with DN and 0.9% in males without DN; in females, 6.8 and 0.6%, respectively. Genetic correlation analysis was performed to determine the genetic interrelation between DN and CMM. In general, the genetic correlation coefficient was 0.9; i.e., predisposition to DN and CMM is determined by common genes for 90%. The frequency and distribution of constitutive fragile sites in chromosomes of peripheral lymphocytes was studied by the method of principal components for discrete variables. The site 1p22 is responsible for variability of the traits CMM and DN for 98.5%. On the one hand, this suggests that one of the supposed genes for CMM can be located at 1p22; on the other hand, CMM and DN are likely to have a common genetic determination or to be very tightly linked. Estimates of risk for the development of CMM in patients' relatives are given with reference to the variants of CMM manifestation and presence of DN.

Epidemiologic and clinical genetic data on cutaneous malignant melanoma (CMM) are presented. The incidence of CMM in Moscow from 1983 to 1987 was analyzed. Cumulative incidence (cumulative risk) was calculated for various life periods on the basis of estimates for various age groups, which were used as population frequencies. By the age of 85, these frequencies were 0.35% for males and 0.38% for females. Among relatives of patients, the incidence of CMM was 1.420 +/- 0.498% for males and 1.110 +/- 0.348% for females; i.e., the incidence exceeded the population frequency by a factor of 3 or 4. As a whole, the familial frequency of cancer was equal to 13.3% for male probands and 14.2% for female probands, i.e., more than three times higher than the population frequency. The data obtained formed the basis for the development of CMM classification. hereditary and nonhereditary variants of cutaneous melanoma were identified. Familial cases and CMM that occurred against the background of inherited disease or syndromes were classified as hereditary variants of CMM; taken together, they accounted for 38.8%. The data provided grounds for identification of families at increased risk for the development of CMM.

A study of 11 immunogenetical blood systems (HLA-A, B C, DR; ABO; Rh-Hr; MNSs; Kidd; Kell-Chellano; Duffy; Lewis; Diego; Gm; Inv) involving 59 antigens was performed in patients of Armenian nationality with lymphogranulomatosis (LGM). Pathogenic associations of HLA, MNSs and Duffy systems with LGM were established. Positive correlations were found (p < 0.001) with HLA phenotypes DR-8, B-14, B-21, SS, Fy(a+b-). These phenotypes have significant correlation with LGM (RR = 4.7-2.1) and can be considered as genetic markers of LGM in the Armenian population.

The study of morphological and biological criteria of laryngeal squamous cell carcinoma in 81 patients proved essential in the disease prognosis. In grade I malignancy 90 +/- 6.7% of patients were 3 years free of recurrences and metastases, in grade 11 - 76 +/- 8.6%, in grade III - 50 +/- 15.8%. Aneuploid laryngeal tumors produced recurrences 6 times more frequently than diploid ones. 3-year recurrence--and metastases-free survival was reported in 88.7 +/- 6.3% of patients with diploid and 59.3 +/- 7.7%. 7% with aneuploid tumors (p < 0.05).

Complex clinical-genealogical and genetic study of 261 patients with breast cancer (BC) was carried out in Kiev region. It was demonstrated that the multifactorial origin of BC was of first importance in this population. The share of genetic component in the susceptibility to BC comprise 55.68 +/- 2.44%. Risk of the origin of malignant tumors in progeny was calculated.

Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the cranial, spinal and peripheral nerves with a high frequency of mutation in the neu proto-oncogene. To establish the requirement for such mutation in tumorigenesis of Schwann cells, spontaneous schwannomas from BD-VI strain rats were evaluated for transforming mutations in the transmembrane domain of the encoded protein for the neu proto-oncogene. Whereas all five schwannomas induced by ENU showed T/A transversions in codon 2012 of neu oncogene upon analysis by selective oligonucleotide hybridization and dideoxy sequencing of polymerize chain reaction amplified products from paraffin sections, only one of nine spontaneous schwannomas from untreated rats exhibited the same mutation. Examination of tumours for mutation in codon 12 of Ki-ras proto-oncogene revealed normal alleles. Our conclusions based on these data are that the high frequency of mutations in neu in ENU-induced tumours appears to be attributable to the carcinogen or to the period of development at which exposure occurred, and that transforming mutations of the transmembrane domain of neu, are not required for tumorigenesis of the Schwann cell.

Main advantages of the cytological method are demonstrated: possibilities of obtaining material from areas which are hardly accessible for open biopsy, investigation of bone tumor before or during the operation, etc. Detailed biological characteristics of tumor cells by means of DNA-flow cytometry, roentgenological and clinical data help to establish correctly a morphological variant of bone tumor and thus to choose an adequate therapeutical method.

Polymorphism of exon 2 of the BoLA-DRB3 gene was investigated by the PCR-RFLP method in a sample of healthy and leukemia-afflicted Black Pied cattle. Allele variety was studied and allele frequencies were determined in a total sample and in the two groups. Alleles mediating resistance (BoLA-DRB3.2*11, *23, and *28) and susceptibility to leukemia (DRB3.2*22, *24, *16, and *8) were revealed in Black Pied cattle. The dominant type of inheritance of the disease resistance was confirmed. On the basis of original and published data obtained earlier for Holstein-Friesian cattle, a conclusion was made about the universal character of the spectrum of BoLA-DRB3 alleles providing resistance and susceptibility to leukemia.

G11 mouse cells and SH2 rat cells transformed with simian adenovirus SA7 DNA showed inheritable oncogen-specific phenotypic normalization when treated with sense and antisense oligonucleotides complementary to long RNA sequences, plus or minus strands of the integrated adenovirus oncogenes E1A and E1B. Transitory treatment of the cells with the oligonucleotides in the absence of serum was shown to cause the appearance of normalized cell lines with fibroblastlike morphology, slower cell proliferation, and lack of ability to form colonies in soft agar. Proliferative activity and adhesion of the normalized cells that established cell lines were found to depend on the concentration of growth factors in the cultural medium. In some of the cell lines, an inhibition of transcription of the E1 oncogenes was observed. The normalization also produced cells that divided 2 - 5 times and died and cells that reverted to a transformed phenotype in 2 - 10 days. The latter appeared predominantly upon the action of the antisense oligonucleotides.

The nucleolus organizer region activity and the level of acrocentric chromosome association in cultured peripheral blood lymphocytes was studied in patients with endometrial glandular hyperplasia and endometrial cancer. The number of active nucleolus organizer regions and the frequency of 13 and 21 acrocentric chromosome associations was higher in patients with endometrial cancer.

45 adrenal cortex adenomas were examined for morphological atypia after adrenalectomy. The majority of clear-, dark- and mixed cell adenomas are characterized by tissue atypia in the form of alveolar-trabecular structure. Adenoma heterogeneity is manifested by cellular polymorphism of a poor, moderate and high degree. It is suggested to distinguish adenomas formed of large, giant and multinuclear cells from dark cell adenomas and to consider them as a special independent giant cell variant.

Cytogenetic effects of ultra low doses of nitrosomethylurea in the range 10(-12)-10(-17) mol/(kg x day) on the chromosome structure were studied in the Ehrlich tumor and leucosis L-12110 cells. It was shown that nitrosomethylurea at an ultra low dose of 10(-17) mol/(kg x day) induces chromosome aberrations in the cells of the both studied tumors after a single and multiple injections to random bred and linear animals. The recorded effect suggests that with the decrease of therapeutic dose by 13 orders of magnitude the cytogenetic activity of the drug decreases by no more than one order of magnitude.

The level of chromosomal aberrations in cultured blood lymphocytes from patients with hyperplasia, atypical hyperplasia of endometrium and endometrial cancer was studied. Chromosomal aberration frequency significantly increased up to 5.000 +/- 00.47% in patients with atypical and endometrial hyperplasia and to 5.21 +/- 00.53% in patients with endometrial cancer in comparison to 0.67 +/- 0.21% in the control. All indices were more pronounced in endometrial cancer patients with pathology in pedigree.

Macromolecular adhesion factors (MAFs) were obtained from the liver of mice with a genetic predisposition for spontaneous hepatoblastomogenesis (CBA) and of resistant mice (C57B1). The MAFs from the liver of both strains are similar in their chemical nature and represents a complex of phosphoglycopeptides with a molecular mass of 20-40 kDa and glycosaminoglycans. The discovered basic difference in the biological effect of MAFs of these strains on the adhesion of hepatocytes appears to be due to disturbances of MAF glycosylation in CBA mice, which cause changes in the spatial-functional organization of the adhesion site in the hepatocytes.