The microspectrometric investigation used 5- and 8 microns-thick histological specimens, stained after Feulgen, and the following equipment: scanning integrating microspectrophotometer (1,080); TV-image analyzer (70). Interphase nuclei of normal growth tissue, mild and moderate dysplasia, atypical proliferation and carcinoma were investigated using bioptical material from the larynx, cervix uteri, endometrium, stomach, large bowel, prostate and breast. The weighted mean index of DNA accumulation in nuclei as well as the "index of clonal proliferation" (ICP)--ratio of average DNA index for carcinogenesis stage in question and normal tissue index--suggested by the author, were measured. Malignant transformation was characterized by the following ICP values: mild and moderate dysplasia--less than 1.4; intraepithelial neoplasia--2.2 and carcinoma and adenocarcinoma--3.3 and higher. Microspectrophotometric analysis of Feulgen-DNA yields reliable data on ICP in malignant tissue which can be used for clinical purposes in treatment and prognosis of malignant disease.

Methylation is a modification that changes the structure and functional status of DNA. Hence it is interesting to study the effect of methylation on basic processes occurring in living cells. In this review, the role of DNA methylation in recombination, replication, transcription regulation, imprinting, tumorigenesis, and tumor progression is considered.

There were examined 94 patients, aged from 22 to 68 years, with myasthenia, in whom morphological changes of thymic gland were revealed. In 89% of observations there was established the infectioning by cytomegalovirus, in 10%--hepatitis B, in 9%--hepatitis C. In 5% of patients there were observed coexistence of cytomegaloviral infection and hepatitis. In all the patients the trustworthy increase of the chromosomal aberrations frequency in comparison with spontaneous level of mutation was revealed. High diagnostic validity of chain reaction with polymerase in the viruses persistence determination was noted. The results of investigation of serous immunoglobulins to the virus neutralizing antibodies ratio may be applied for the indications elaboration in the lymphosorption and immunocorrection application in patients with myasthenia more than 4 years in course.

The cytotoxic action of melatonin on DNA synthesis was studied in short-term human tumor tissue cultures. Twenty tumors (ovarian, renal, colorectal, gastric, skin, testicular, thyroid, adrenal gland, endometrial, cervical uterus ones, and melanoma) were isolated from patients at surgery. The effect of melatonin (concentrations of 5 x 10(-5) M to 5 x 10(-13) M on the level of 3H-thymidine incorporation into tumor tissue DNA (4-hour exposure) was evaluated. After exposure, 3H-thymidine was added to the medium for an hour. The quantity of DNA was determined in the hydrolysate by spectrometry; the level of 3H-thymidine incorporation into DNA was radiometrically evaluated by a scintillation counter. The quantity corresponding to 3H-thymidine incorporation per unit of DNA was determined. The control group and the melatonin-treated groups were compared by ANOVA. Melatonin inhibited DNA synthesis in 11 (55%) of the 20 tumors and was ineffective in 9 (45%) of the 20 ones. Melatonin-sensitive tumors were as follows: endometrial CA (33% vs 75% inhibition, p < 0.01), gastric CA (71% inhibition, p < 0.05), adrenal gland CA (38% inhibition, p < 0.01). Ovarian, cervical, skin CA and melanoma were unresponsive to melatonin. Renal cell CA, colonic and rectal CA were sensitive in some cases. In sensitive tumors, melatonin was effective even at concentrations of 5 x 10(-13) M to 5 x 10(-7) M. Thus, melatonin has an oncostatic effect on some human tumors in vitro occasionally at physiological concentrations.

After the accident at the Chernobyl nuclear power plant, a considerable increase in the incidence of thyroid cancer among children in Belarus was observed. In the present study, the frequency of the c-ret protooncogene rearrangements in samples of thyroid carcinomas resected and diagnosed in 1998 from individuals in Belarus was investigated. The ret/PTC1 oncogene was detected in 19% of the samples, and the ret/PTC3r1 oncogene, in 14%. The number of ret/PTC1 rearrangements observed in tumor cells from the patients whose age at the time of the accident was from 1 to 10 years, was greater compared to those whose age at the time was from 10 to 20 years, irrespective of the year of surgery (1996 or 1998). The majority of the patients with ret/PTC3r1 rearrangements lived in Gomel oblast, which was contaminated by the Chernobyl meltdown.

To compare forms of chronic lymphoid leukemia (CLL) regarding mutational status of immunoglobulin variable genes.

A strong connection is known to exist between initiation/promotion of endometrial cancer and excess of estrogens. Therefore, participation of certain alleles of genetic polymorphisms in steroid biosynthesis or metabolism may be responsible for predisposition to the disease. The present study, comparing CYP19 (aromatase) gene polymorphism in 85 patients and 110 healthy females, pointed to a more frequent occurrence of relatively longer alleles (A6 and A7) of the CYP19 gene in the former group. Furthermore, precisely those genotypes co-occurred more frequently with elevated blood levels of estradiol and testosterone in postmenopausal patients. Hence, CYP19 gene polymorphism may be regarded as a factor of genetic risk for endometrial carcinoma.

Associations of a new human herpesvirus type 8 (HHV-8) with different forms of Kaposi's sarcoma (KS) in Russia have been studied. Search for this virus genetic information has been carried out in biopsy specimens of benign and malignant tumors other than KS, and probable sites of HHV-8 latency in human body have been checked. HHV-8 sequences were detected by polymerase chain reaction (PCR). HHV-8 sequences were most often detected in idiopathic (80.6%), AIDS-associated (80%), and immunosuppressive (100%) KS. The results indicate a selective association of HHV-8 with KS. No probable sites of the virus latency were detected in peripheral blood cells of patients with KS and in the prostate of patients with chronic prostatitis. The only exception was the husband of a patient with KS: HHV-8 sequences were detected in his prostatic secretion by nested PCR.

The synthetic gene of bradykinin was built into the retrovirus vector pPS-3-neo under the guidance of LTR promotor, followed by pPS-3-neo (brd) vector transfection of strain 293 cells. The physiological activity of the expressed bradykinin was tested on cultured neonatal rat cardiomyocytes. The culture medium of strain 293 cells transferred by pPS-3-neo (brd) produces a positive chronotropic effect that is directly related to the time parameters of preparation of recombinant bradykinin, which are comparable with the curve of chronotropic effect of synthetic bradykinin at concentrations of 10(-17) to 10(-16) M. The control of bradykinin "gene" expression was due to the lack of chronotropic responses of cardiomyocytes to the kinin receptor blocker parmidine and the transfection of strain 293 cells with the retrovirus vector without bradykinin "gene".

The inner cytosine methylation was analyzed in the CCWGG sequences of the 5'-terminal region of the human calcitonin gene from peripheral blood and bone marrow cells in various forms of leukemia. Since these sequences remain nonmethylated both in norm and in various leukemia forms, the CpG dinucleotide hypermethylation of the 5'-terminus of the human calcitonin gene, characteristic for the development of leukemias, does not spread over adjacent CpNpG sequences.

46 samples of squamous-cell lung carcinoma (SqCLC) from surgical patients were examined for biomolecular tumor markers (pancytokeratins, c-myc, p53, bcl-2, Bax, Ki-67, IGF-system) and apoptosis. Keratinization appeared an independent from apoptosis type of programmed cell death. It relates to cell death by differentiation, is followed by accumulation of c-fos, c-myc, Bax, IGF-II, IGFBP-2, IGFBP-5 this indicating their involvement in the regulation of this process. High level of apoptosis does not determine positive prognosis of the neoplastic process as it is not a single variant of programmed cell death in SqCLC. Malignant grade of SqCLC depends upon correlation between the proliferative processes and various types of cell death. Better prognosis of well and moderately differentiated SqCLC (as compared to poorly differentiated carcinomas) may be due to the fact that high proliferative activity of the tumor cells is balanced by their death by keratinization.

Clinical, morphological and cytogenetic investigations were done in those patients with leukocytosis having become victims of the Chernobyl catastrophe. Of these (n = 10), six patients demonstrated chromosomal abnormalities. In the study made at a later date in six patients with cytogenetic abnormalities, five patients were found to have chronic myeloproliferative disorders, with four cases presenting with chronic myeloid leukemia and one patient having osteomyelofibrosis.

A general principle of the maintenance of malignant growth in all types of tumors has been formulated. According to this principle, stochastic but continuous death of some tumor cells due to the inherent genetic instability of their genome (fragility of chromosomes) is the main event stimulating tumor growth. The dead cells trigger a complex multicomponent process of wound healing expressed as further proliferation of living tumor cells, angiogenesis, stimulation of cell migration, and other events. Stimulation of the proliferation of living cells leads to further death of cells and, as a result, to further stimulation of the system of wound healing, etc. Thus, the tumor sacrifices a small amount of dying cells to stimulate proliferation of all its other cells. It is proposed that the nature of the genetic instability of malignant cells is related to the appearance of an uninemic structure in some regions of chromosomes, in whole chromosomes, or in whole genomes. The author bases his statements on the binemic structure of chromosomes, which has already been experimentally and theoretically substantiated. Uninemic regions have an exceedingly high frequency of spontaneous chromosome aberrations due to blockage of the mechanism of underlying repair of the DNA double break in the absence of a second DNA copy. Possible approaches to a search for more efficient methods of therapy are discussed.