Effects of specific monooxygenase and oxidase inhibitors on the activation of 2-aminofluorene by plant cells.
Using specific inhibitors, a plant cell/microbe coincubation assay was employed to investigate biochemical mechanisms of plant activation. The biological endpoints of mutation induction, inhibition of mutagenicity and viability of the plant-activating system as well as viability of the microbiological indicator were simultaneously assayed from the same reaction tube. We investigated six inhibitors of monooxygenases and oxidases (diethyldithiocarbamate, methimazole, metyrapone, (+)-catechin, 7,8-benzoflavone and potassium cyanide). The activation of 2-aminofluorene by TX1 cells was mediated by an enzyme system(s) that was inhibited by microM amounts of diethyldithiocarbamate or 7,8-benzoflavone. (+)-Catechin (at low concentrations) or methimazole enhanced the activation of 2-aminofluorene while higher concentrations of (+)-catechin were inhibitory. These data indicate that a significant pathway of the plant activation of 2-aminofluorene is via a cytochrome P-448-type N-hydroxylase. The presence of a FAD-dependent monooxygenase was not detected.
Wagner
E D
ED
Institute for Environmental Studies, University of Illinois, Urbana 61801.
Gentile
J M
JM
Plewa
M J
MJ
D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005449:Fluorenes / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009152:Mutagenicity Tests; D010944:Plants / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects
D001571:Benzoflavones; D005449:Fluorenes; C012177:2-aminofluorene; D008713:Methimazole; C011512:alpha-naphthoflavone; D002392:Catechin; D004050:Ditiocarb; D006899:Mixed Function Oxygenases; D011190:Potassium Cyanide; D008797:Metyrapone