Dietary selenium deficiency causes decreased N-oxygenation of N,N-dimethylaniline and increased mutagenicity of dimethylnitrosamine in the isolated rat liver/cell culture system.
Male Wistar rats were fed diets of varying selenium content in order to obtain selenium-deficient and selenium-supplemented rats. After 5-6 weeks on the respective diet, the rats were used to investigate how selenium influences the effect of dimethylnitrosamine (DMN) on some liver enzymes and related reactions. The selenium-dependent glutathione peroxidase activity in postmicrosomal supernatant from liver was about 1% in selenium-deficient rats as compared to selenium-supplemented rats or rats fed a standard diet. The highest DMN-demethylase activity was observed in postmitochondrial supernatant from selenium-deficient rat liver, and the lowest in selenium-supplemented rats. No dietary effect was observed on hepatic microsomal cytochrome P450 levels. C-Oxygenation of N,N-dimethylaniline (DMA) was not affected by the selenium level. On the other hand, selenium deficiency seemed to reduce N-oxygenation of DMA. The mutagenicity of DMN in Chinese hamster V79 cells after metabolic activation by the isolated perfused rat liver, was approximately doubled when selenium-deficient livers were used as compared to selenium-supplemented livers and livers from rats fed a standard diet. A negative correlation between DMA-N-oxygenation and mutagenicity from DMN was observed, whereas no correlation between DMA-C-oxygenation and mutagenicity from DMN was found.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010100:Oxygen; D051381:Rats; D012643:Selenium / Q000172:deficiency*
D000814:Aniline Compounds; C015157:N,N-dimethylaniline; D003577:Cytochrome P-450 Enzyme System; D005979:Glutathione Peroxidase; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D012643:Selenium; D004128:Dimethylnitrosamine; D010100:Oxygen