[INFLUENCE OF DOXORUBICIN AND ETOPOSIDE ON THE CD 95 MEDIATED APOPTOSIS IN EBV INFECTED LYMPHOMA CELLS BL-41 AND DG-75].

The aim of work was to study the effect of anticancer drugs on the process of CD 95 mediated apoptosis in BL-41 and DG-75 infected with Epstein-Barr virus. Studies of the effect of anticancer drugs "Doxorubicin" "Ebewe" and "Vepesid" (Etoposide) on the apoptosis in EBV infected cells using cytomorphological methods, spectrophotometry and PCR carried out. The influence of the tested drugs in cell culture was assessed by calculating the CC50. It was shown that it was 20 µg ml both for Etoposide and for Doxorubicin in the case of cell line DG-75. BL-41 cells were more sensitive to the tested drugs. CC50 was 5 µg/mI. PCR method showed that in the studied cell lines active accumulation of EBV DNA took place. In 24 hours after infection in the DG 75 + EBV system 20 µg/ml Doxorubicin provoked apoptosis in 89% of cells, and Etoposide-induced apoptosis was 35%. Cell culture BL-41 was equally sensitive to both drugs. At the same time, in the EBV super infected cells + Doxorubicin only 10% of apoptotic cells were detected. The obtained data prove the impact of viral infection on the sensitivity of lymphoma cells BL-41 and DG-75 to tested anticancer drugs.

Study of adenovirus reproduction in different lymphoblastoid cell lines.

The comparative characteristic of the reproduction of adenovirus serotypes 2 and 5 (HAdV-C2 and -C5) in the various lymphoblastoid cell lines were studied. Rapid formation of infectious viruses in Raji, MP-1, Namalwa, BJAB, MT4 and Jurkat cells was marked and it was found to be close to the level of viruses during reproduction in permissive Hep-2 epithelial cells. Yield of infective adenovirus was low in B95-8 cells, which were chronically infected with Epstein-Barr virus (EBV). This may indicate the interference of Ad with EBV during super-infection. The CEM cells produced chronically low amounts of human adenovirus serotype 2.

Inhibitors of Epstein-Barr virus reproduction--ribonucleosides of 3-substituted 1,2,4-triazino[5,6-b] [1,4] benzothiasines.

Studying of antiviral effect of condensed triazine derivatives--3-oxo- triazinobenzothiazine (the preparation No 1), its ribonucleoside (the preparation No 3) and ribonucleoside of its 3-thio-analogue (the preparation No 2) on reproduction of Epstein-Barr virus (EBV) in lymphoblastoid Raji cells is reported in present work. The cytotoxic action of these preparations on test cells was determined and CC50 index was 125 microg/ml for the preparation No 1, for preparation No 2 - 625 microg/ml, and for preparation No 3 - 750 microg/ml. Antiviral activity of the preparations was tested by inhibition level of accumulation of viral DNA in the cell culture, and effective concentration (EC50 index) was determined for each preparation. EC50 constituted 1 microg/ml for each triazinobenzothiazines. Selectivity index (SI) was 125 for preparation No 1, for preparation No 2 - 625, and for preparation No 3 - 750. The obtained results of studying of triazinobenzothiazines as inhibitors of EBV-infection support their high antiEBV activity and can be interesting for further investigations.

Elaboration of optical immunosensors based on the surface plasmon resonance for detecting specific antibodies and antigens of Epstein-Barr virus and human adenovirus.

The study of antigen-antibody interaction on the model of Epstein-Barr virus (EBV) and second type adenovirus (Ad2) based on the surface plasmon resonance (SPR) was carried out. Kinetic and concentration dependences between virus antigens and specific antisera to them at different pH were determined. Experimental samples of biosensors for the detection by SPR method of virus (EBV and Ad2) antigens using monospecific antibodies, immobilized on the surface of gold, and also for detection of specific antibodies in the blood sera of patients with EBV or adenovirus infection were elaborated