title: Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects.
abstract: The general toxic and hepatocarcinogenic effects of diethylnitrosamine after stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than in response to diethylnitrosamine without preinduction. Injection of diethylnitrosamine to suckling ICR mice after TCPOBOP induction of cytochrome P450 2e1 activity led to development of 2-fold lesser number of tumors and pretumorous nodes in the liver in comparison with animals injected with diethylnitrosamine without induction. These data indicated that metabolism stimulation reduced the general toxic and hepatocarcinogenic effects of diethylnitrosamine.
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia. pathol@inbox.ru.
authors.forename: S I
authors.initials: SI
authors.lastname: Il'nitskaya
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: V I
authors.initials: VI
authors.lastname: Kaledin
authors.affiliation: Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia.
authors.forename: L A
authors.initials: LA
authors.lastname: Bogdanova
authors.affiliation: Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia.
authors.forename: T S
authors.initials: TS
authors.lastname: Morozkova
authors.affiliation: Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia.
authors.forename: V I
authors.initials: VI
authors.lastname: Kapustina
authors.affiliation: Research Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.
authors.forename: M L
authors.initials: ML
authors.lastname: Perepechaeva
authors.affiliation: Research Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.
authors.forename: A Yu
authors.initials: AY
authors.lastname: Grishanova
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000378:metabolism* / Q000633:toxicity; D008658:Inactivation, Metabolic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009596:Nitrophenols / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D009596:Nitrophenols; D011725:Pyridines; D004052:Diethylnitrosamine; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D019392:Cytochrome P-450 CYP2E1; C024836:4-nitrophenol
keywords: cytochrome P450 2e1; diethylnitrosamine; hepatocarcinogenesis; toxicity