Effects of nine N-nitroso compounds on the specific radioactivity of liver proteins after injection of [14C]leucine into rats.
We compared the effect of nine N-nitroso compounds, given by gavage to adult rats, on specific radioactivity of the trichloroacetic acid-precipitable liver proteins, 1 hr after the injection of [14C]leucine. The specific radioactivity was decreased by dimethylnitrosamine, diethylnitrosamine, methyl-n-butylnitrosamine, and nitrosomorpholine 5 to 10 hr after their administration; was increased by nitrosopiperidine, dinitrosopiperazine, and methylnitrosourea 5 to 24 hr after gavage; and was unaffected by nitrososarcosine and nitrosodihydrouracil. With dimethylnitrosamine, specific radioactivity was decreased by 10 but not 5 mg/kg. In control rats and rats given injections of either of two nitrosamines, protein specific radioactivity at 60 min after the [14C]leucine injection was 76 to 87% of that at 30 min, indicating some degradation of the proteins at 60 min. The liver:blood ratio of [14C]cycloleucine concentration was unaffected by four nitrosamines, indicating no effect on leucine transport. The effect of the nine compounds was examined on total pool size of free leucine in the liver, at times close to those for the maximum specific radioactivity effect. For these data, we calculated "corrected specific radioactivity," adjusted for changes in pool size. This adjustment is only a first approximation since, for example, the free leucine pool is not uniform with respect to protein synthesis. The four N-nitroso compounds that decreased specific radioactivity also decreased corrected specific radioactivity, even though they enlarged the leucine pool. Of the remaining compounds, two enlarged the leucine pool and three increased corrected specific radioactivity. For all nine compounds, the decrease in specific and correlated with the ability to cause acute liver necrosis. When nitrosodihydrouracil was excluded, the decrease in specific and corrected specific radioactivity was significantly correlated with the reported liver carcinogenicity.
D000818:Animals; D003515:Cycloleucine / Q000378:metabolism; D004052:Diethylnitrosamine / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009336:Necrosis / Q000139:chemically induced; D009603:Nitroso Compounds / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012521:Sarcosine / Q000494:pharmacology; D013997:Time Factors
D009025:Morpholines; D009603:Nitroso Compounds; D010879:Piperazines; D010880:Piperidines; D011506:Proteins; D003515:Cycloleucine; D004052:Diethylnitrosamine; D008770:Methylnitrosourea; D007930:Leucine; D004128:Dimethylnitrosamine; D012521:Sarcosine