A comparison of ascorbic acid excretion with other indicators of nitrosamine hepatotoxicity.
All of the 4 noncarcinogenic nitrosamines (NA) and 4 of 7 carcinogenic nitrosamines examined increased the urinary ascorbic acid output after oral administration to rats. Of the remaining carcinogenic nitrosamines, dimethyl-NA decreased, and diethyl-NA and methyl-n-pentyl-NA only marginally affected ascorbic acid output. All of the carcinogenic nitrosamines, except dipentyl-NA, increased pentobarbital-induced sleeping time (PST), serum glutamic oxalacetic transaminase (SGOT) and produced loss of glycogen and necrosis in the centrologular area of the liver after 1 or 3 oral doses. In contrast, noncarcinogenic nitrosamines and dipentyl-NA shortened PST and had no effect on liver histology (light microscopy) and SGOT. Generally, changes in ascorbic acid output correlated neither with carcinogenicity nor acute hepatotoxicity of known nitrosamines, hence the ascorbic output could not be used to predict the carcinogenicity of unknown or untested nitrosamines.
D000818:Animals; D001205:Ascorbic Acid / Q000652:urine*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000652:urine*; D008099:Liver / Q000473:pathology; D009602:Nitrosamines / Q000009:adverse effects*; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D009602:Nitrosamines; D001219:Aspartate Aminotransferases; D010424:Pentobarbital; D001205:Ascorbic Acid