Rapid oxidative stress induced by N-nitrosamines.
We have investigated the generation of prooxidant state shortly after administration of N-nitrosamines (NA) to rats. N-Nitrosodimethylamine (NDMA) was found to increase ethane exhalation (EE) rapidly in a dose-related manner. EE remained elevated for several days after single doses of NDMA. Similarly, lipid peroxidation (LP) in the liver (measured by four methods) increased rapidly showing a peak 20 min after NDMA dose. The increase of LP was preceded by a decrease in retinol concentration in the liver. N-Nitrosodiethanolamine, too, increased EE and LP in the liver, whereas N-nitrosomethylbenzylamine had no effect. Thus, hepatocarcinogenic NA induced LP in their target tissue, and the LP enhancing effects of NA were not related to their acute toxic effects.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004980:Ethane / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009602:Nitrosamines / Q000494:pharmacology*; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014801:Vitamin A / Q000378:metabolism
D002273:Carcinogens; D008054:Lipid Peroxides; D009602:Nitrosamines; D014801:Vitamin A; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; C014707:nitrosobenzylmethylamine; D010544:Peroxidases; D005978:Glutathione; D004980:Ethane; D004128:Dimethylnitrosamine