[Effect of cell microenvironment on cell functions associated with tumour promotion and progression].

To study the tumour-promotion activity of cell environment the transformed embryonic rat fibroblasts (clone CL-1-1) were transfect to immunodeficient mice then the cells of the formed tumour were cultivated (clone CL-1-1). The cells before and after transplantation were compared by morphology, proliferation activity and gap junction intracellular communications. The clone CL-1 cells proliferated much faster than clone CL-1 cells. The CL-1-1 cells had changed morphology structure and unlike CL-1 the contract inhibition was absent in CL-1-1. The number of CL-1 cells in phase G1 was significantly greater than that of CL-1-1 cells, while the number of CL-1-1 cells in G2/M phases was much more the number of CL-1 cells. The activity of gap junction intercellular communications in both cell types was near the same. It was concluded that cell microenvironment act as a tumour-promoter and tumour progression factor in the case of cell transplantation to immunodeficient mice.

[Intercellular interactions through gap junctions in embryonic stem cells].

The article deals with the last research project of Levon Mikhailovich Chailakhyan devoted to the role of local intercellular interactions in maintaining the pluripotency of embryonic stem cells and in the processes of their spontaneous multitissue differentiation. For performing the project, Levon Mikhailovich organized in 2008 a group of researchers from the Vavilov Institute of General Genetics of the Russian Academy of Sciences and Belozersky Research Institute of Physicochemical Biology of Lomonosov Moscow State University. In the last month of his life, Levon Mikhailovich wrote an article concerned with the first results of the work. At present the work on the project is being continued.

[Ah receptor-independent inhibition of gap junction intercellular communications in hepatoma cell culture 27 by polycyclic aromatic hydrocarbons].

One of the systems that regulate tissue homeostatis is gap junction intercellular communications (GJIC). Inhibition of GJIC is widely used in experiments as a characteristic of tumor promotion. It is accepted that the down-regulation of GJIC is tightly related with the tumor-promoting properties of carcinogens. In this study, the effect of some carcinogenic polycyclic aromatic hydrocarbons on GJIC in cell cultures of hepatoma 27 lacking cytochrome P450 and Ah receptor was investigated. It was shown that inter 6 compounds studied only benzo/a/pyren and 3-methylcholanthrene were able to inhibit GJIC. We have concluded that an unknown factor is present in hepatoma cells and its interaction with some polycyclic aromatic hydrocarbons results in GJIC inhibition. The investigation of mutual effect of benzo/a/pyrene and non carcinogenic benzo/e/pyrene with similar structure has shown that GJIC inhibition by benzo/a/pyrene is at least double stepped.

[Effect of some polycyclic aromatic hydrocarbons on gap junction intercellular communication in hepatoma Hep G2 cell culture]. / Deistvie riada politsiklicheskikh aromaticheskikh uglevodorodov na mezhkletochnye shchelevye kontakty v kul'ture kletok gepatomy Hep G2

Systems regulating tissue homeostasis are gap junction intercellular communications (GJIC). It is accepted that the down-regulation of GJIP has been due to tumor promoting properties of carcinogens. In this study, effects of some carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons (PAH) on GJIC were investigated. Noncarcinogenic PAHs do not influence GJIC function. In dose 5 microg/ml carcinogenic PAHs down-regulated GJIC by 70-100% after a 24 h treatment. Dependent on the structure of PAHs, down-regulation was observed after a 1 h treatment. The methyl group in PAH structure decreased down-regulation of GJIC in 1 h experiments, whereas after a 24 h treatment the down-regulation caused by methyl group either contained or not contained PAH was nearly the same. To clarify the role of Ah-receptor in PAH action on GJIC, the effect of 2,3,7,8-tetrachlorodibezdioxin, a specific ligand of Ah-receptor was studied, which appeared to be insignificant. Benzo/a/pyrene does not influence the functioning of gramicidine channels formed in the phospholipid membrane. This result indicates that PAH action on GJIC is not associated with non-specific destruction of the membrane. Thus, two steps are there in PAH action on GJIC: one is fast and caused by specific interaction of unchanged PAH molecule, the other develops in time and is presumably associated with the formation of active metabolites.

[Highly permeable contacts and electrical characteristics of the tissue of the normal liver and hepatomas. III. Absence of an effect of the tumor promoter phenobarbital on intercellular contacts in the mouse liver]. / Vysokopronitsaemye kontakty i élektricheskie kharakteristiki tkani normal'noi pecheni gepatom. III. Otsutstvie vliianiia opukholevogo promotora fenobarbitala na mezhkletochnye kontakty v pecheni myshi.

The effect of phenobarbital--a specific promoter of hepatocarcinogenesis--on electrical parameters of mouse liver cells in vitro has been investigated using the conventional microelectrode technique. No alterations were found in cell membrane potentials, input resistances and electrical coupling coefficients measured either immediately after a short-term incubation of isolated livers in the presence of phenobarbital, or after a long-term treatment of the animals per os with the promoter for several weeks.

[Highly permeable contacts and the electrical characteristics of normal liver tissue and hepatomas. II. A structural model and calculation of the cell membrane permeability of induced mouse hepatomas]. / Vysokopronitsaemye kontakty i élektricheskie kharakteristiki tkani normal'noi pecheni i gepatom. II. Strukturnaia model' i raschet pronitsaemosti membran kletok indutsirovannykh gepatom myshi.

The values of specific resistances of non-junctional (Rm) and junctional (Rj) membranes of mouse induced hepatoma cells were calculated with the aid of the syncytium theory equations and on the basis of the previously measured input resistances and electrotonic potential spread curves. A three-dimensional model with cable element length equal to two cell diameters, with the length constant value of 600 mkm, and with three contacts per cell was used for calculations. For this model, Rm and Rj were found to be 3300-5600 Ohm . cm2 and 2 . 10(-2) Ohm . cm2, respectively. For the three-dimensional model of normal liver, Rm and Rj amounted to 2400-7200 Ohm . cm2 and 6.5 . 10(-2) Ohm . cm2, respectively.

[Highly permeable contacts and the electrical characteristics of normal liver and hepatoma tissue. I. The highly permeable contacts in induced mouse hepatomas]. / Vysokopronitsaemye kontakty i élektricheskie kharakteristiki tkani normal'noi pecheni i gepatom. I. Vysokopronitsaemye kontakty v indutsirovannykh gepatomakh myshi.

With the aid of intracellular microelectrodes some electrical characteristics of mouse liver were studied in early and late stages of chemical carcinogenesis. In early stages of carcinogenesis as well as in induced hepatomas, the membrane potentials of the cells, the input resistance of cell system and the electrotonic potential distribution in tissue did not differ from the corresponding values in normal liver. It is concluded that at all the stages of carcinogenesis electrical coupling in liver remains unaltered. It is proposed that high-permeable intercellular junctions may play a significant non-specific role in tissue malignization process.

[The electrical structure of normal liver tissue]. / Elektricheskaia struktura tkani normal'noi pecheni

The electrical coupling between cells of mouse liver was investigated in vitro. The membrane potential of liver cells is 15--30 mv immediatly after dissection, and increases to 40--48 mv within 4--7 hours. This level of membrane potential is constant during the next 2--3 hours. The mean input resistance varies within 189+/-9 and 613+/-+25 kohm to be higher in preparations examined in summer than in winter time. The cytoplasm of liver cells is equipotential. The reducing of potential from intracellular source is not exponential. This potential distribution is well approximated by a solution for the two-dimentional model of the liver lamella, when characteristic length is 500 mcm. On the basis of this model the outher membrane resistance and functional membrane resistance were found to be 700-2100 and 1.2 ohm-cm2, resp.