Vol. 45 (2003), ¹ 1, p. 51-58
EFFECT OF SOME POLYCYCLIC AROMATIC HYDROCARBONS ON GAP JUNCTION INTERCELLULAR COMMUNICATIONS IN HEPÀÒÎÌÀ HEP G2 CELL CULTURE

Yu. Yu. Sharovskaya,1 T. I. Rokitskaya,1 V. A. Koblyakov 2

1 A. N. Belozersky's Institute of Physico-Chemical Biology of Moscow State University, and 2 Institute of Carcinogenesis, N. N. Blochin's Russian Cancer Research Center RAMS, Moscow;
1 e-mail: vakob@crc.umors.ru

Systems regulating tis ue 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 carci logenic 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 distruction 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.

Key words:  hepatoma, gramicidine channels, carcinogens, polycyclic aromatic hydrocarbons, gap junction


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