[Methylation of the putative tumor suppressor gene, RASSF1A, in primary cervical tumors]. / Metilirovanie predpolagaemogo gena-supressora RASSF1A v opukholiakh sheiki matki.

The methylation level of 13 CpG-dinucleotides in the promoter region of the putative tumor suppressor gene RASSF1A (3p21.31) was analyzed in HPV-positive squamous cell carcinomas of cervix using methyl-sensitive restriction endonuclease analysis followed by PCR. The methylation from 3 to 13 CpG-dinucleotides was observed in 64% (25/39) tumors, 22% (2/9) morphologically normal tissues adjacent to tumors (P = 0.0306) and in 2 from 3 leucocytes of peripheral blood of patients. The methylation of these CpG-dinucleotides was absent in DNA of healthy donor leucocytes (0/10). Methylation level of the examined fragment of the RASSF1A promoter region was significantly higher in tumors of patients with lymph node metastases in comparison to tumors of patients without metastases (P = 8.5 x 10(-12)). The methylation frequency of RASSF1A gene was in two times higher than hemi- and homozygous deletion frequency at the region of location of this gene (chromosome 3p21.31), determined earlier. These data suggest that methylation of the RASSF1A gene is one of the main ways of this gene inactivation in HPV-positive cervical squamous cell carcinomas. The methylation of the RASSF1A gene is an early event in genesis of tumor and the level of methylation increased with tumor progression.

[Search for HHV-8 associated diseases reservoir and spread paths of HHV-8 in Russia]. / Poiski HHV-8-assotsiirovannykh zabolevanii, rezervuara i putei rasprostraneniia HHV-8 v Rossii.

Summarized in the paper are study results of human herpesvirus type 8 (HHV-8) and of its association with Kaposi's sarcoma (KS). The data obtained denotes that the share of individuals producing the antibodies to HHV-8 in a majority of studied patients was low and ranged form 0 to 5.5%, which is indicative of a low degree of the virus spread in population. At the same time, a high share of persons with antibodies to HHV-8 was detected among HIV-infected homosexuals (71.4%), kidney recipients (26.0%) and among AIDS-KS patients (78.6%). It was also unexpectedly high among patients with T- and B-cell lymphomas (50%), encephalopathy (27.3%) and with stomach cancer (41.8%): the appropriate parameters were 7-12-fold higher versus healthy subjects. The HHV-8 markers, i.e. virus specific antibodies and/or nucleotide sequences of the virus, were detected in blood serum and ejaculate of a significant number of patients with different pathologies of the prostate. Such detection of viral markers in the above categories of patients is suggestive of that sexual contacts with such patients are decisive for the HHV-8 spread in population.

[Antibodies to herpesvirus type 8 in Kaposi's sarcoma patients and controls in Russia]. / Antitela k gerpesvirusu tipa 8 u bol'nykh sarkomoi Kaposhi i lits kontrol'nykh grupp v Rossii.

The purpose of the present study was to investigate the HH-8 seroprevalence among patients with Kaposi's sarcoma (KS), melanoma and gastric carcinoma (GC) as well as among renal recipients and blood donors. The obtained data revealed a high percentage of seropositive KS patients, which ranged from 83.6% in the classical disease type to 68.8% and to 71.4% in the immunosuppressive and AIDS-associated disease types, respectively. On the whole, the positive humoral response to HHV-8 reliably correlated with the positive findings if the viral genetic information in tumor tissue samplings. An unexpectedly high percentage of seropositive persons was found among the GC patients (41.8%) and among the renal recipients (26%), which is apparently predetermined by the immunosuppressive condition of such patients. Seroprevalence was found only in 4% of blood donors. Thus, the obtained data make it possible to conclude that KS cases, as diagnosed in Russia, are tensely associated with HHV-8 in spite of a low virus spread among the healthy population. Patients with pathology concomitant with a pronounced immunosuppression are characterized by a high prevalence of HHV-8 and belong to the category of persons with a KS risk.

[PCR diagnosis of sequences of a novel human herpes virus type 8 in patients with Kaposi sarcoma in Russia]. / PTsR-diagnostika posledovatel'nostei novogo gerpesvirusa cheloveka 8-go tipa u bol'nykh sarkomoi Kaposhi v Rossii.

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.

[Effect of ascorbic acid on the frequency of the occurrence of colchicine- and methotrexate-resistant colonies]. / Vliianie askorbinovoi kisloty na chastotu poiavleniia kolonii, ustoichivykh k kolkhitsinu i metotreksatu.

The influence of ascorbic acid (vitamin C) on the frequency of occurrence of colchicine- and methotrexate-resistant colonies of Djungarian hamster DM-15 cells was studied the number of resistant cells was found to increase 2.9-19.8-fold. The genetic effect of using high vitamin C doses is discussed.

[Induction of gene amplification in Djungarian hamster cells by various chemical carcinogens]. / Induktsiia gennoi amplifikatsii v kletkakh dzhungarskogo khomiachka nekotorymi khimicheskimi kantserogenami.

The influence of 9 different carcinogens on gene amplification was studied in DM-15 Djungarian hamster cells. The effect was assessed by resistance to colchicine or methotrexate. It was found that tumour promotors (12-0-tetradecanoylphorbol-13-acetate (TPA), mezerein, tween-80) and some carcinogens possessing both initiating and promoting activity (20-methylcholanthrene, 7,12-dimethylbenz(a)antracene, aflatoxin B1) dramatically increased the number of colchicine and methotrexate-resistant cells. 4-0-methylTPA, a non-promoting analog of TPA, and alkylating carcinogens (ethylmethanesulphonate and nitrosomethylurea) did not induce gene amplification. It was suggested that the ability of carcinogens to induce gene amplification correlated with their ability to induce the second promotion stage.