INVESTIGATION OF THE ROLE OF DEMETHYLATION AND DENITROSATION ACTIVITIES OF CYTOCHROME P-450 IN PROCESS OF N-NITROSODIMETHYLAMINE-INDUCED APOPTOSIS OF RAT’S PERITONEAL MACROPHAGES

L.N. Smerdova, S.V. Snoz, N.P. Dmitrenko

It had been shown in vitro, that N-nitrosodimethylamine (NDMA) evokes the death of rat’s peritoneal macrophages depended on incubation time. Activated by BCG peritoneal macrophages synthesize NO more intensively and they are more stable to NDMA cytotoxic effects than nonactivated. Under NDMA influence in activated macrophages denitrosation activity decreases, N-demethylation activity increases, but in nonactivated macrophages denitrosation activity increases and N-demethylation activity doesn’t change essentially. Pyrazole importantly oppresses the NDMA biotransformation and rises the stability to its cytotoxic effects of activated and nonactivated macrophages. Activated macrophages’ stability to the NDMA cytotoxic effects increases, when 2 mM arginine is in the incubation medium; in present of 0,5 mM NO covalent acceptor this stability decreases. The obtained results are discussed with position, that NDMA cytotoxic effects connect with its biotransformation, mainly denitrosation, and depend on state of NO metabolism in cell. The activities of isoforms of cytochrome P-450 and, consequently, the character of xenobiotics’ biotransformation on the organism may happen the changes in the process of apoptosis,

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