Effect of dietary selenium on biotransformation and excretion of mutagenic metabolites of N-nitrosodimethylamine and 1,1-dimethylhydrazine in the liver perfusion/cell culture system.
The mutagenicity of N-nitrosodimethylamine (NDMA) and 1,1-dimethylhydrazine (UDMH) has been studied in an isolated liver perfusion/cell culture system. The liver donors, male Wistar rats, were either selenium (Se)-deficient or had a physiologically adequate Se status (Se-supplemented). Mutagenicity was measured in perfusate and bile with Chinese hamster V79 cells as the genetic target. Se deficiency increased the mutagenic effect of NDMA in the perfusate, whereas no mutagenicity was detected in the bile of either Se-deficient or Se-supplemented livers. No significant increase in the mutagenicity of UDMH was seen in the perfusate with Se deficiency, but the bile became mutagenic. Se deficiency thus increased the mutagenicity of both NDMA and UDMH: with NDMA, the effect was observed in the perfusate, and with UDMH, in the bile.
Beije
B
B
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Olsson
U
U
Onfelt
A
A
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004032:Diet; D004127:Dimethylhydrazines / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008763:Methylhydrazines / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D012643:Selenium; D004128:Dimethylnitrosamine