Diethyldithiocarbamate suppresses the plant activation of aromatic amines into mutagens by inhibiting tobacco cell peroxidase.
Diethyldithiocarbamate is an antimutagen and repressed the activation of promutagens by plant systems. Earlier work implicated the involvement of tobacco cell (TX1) peroxidases in the plant cell activation of aromatic amines. We now present data that diethyldithiocarbamate represses the activation of 2-aminofluorene and m-phenylenediamine by inhibiting intracellular TX1 peroxidases under in vivo conditions. Concentrations of diethyldithiocarbamate that caused a 50% repression of TX1 cell activation of 2-aminofluorene and m-phenylenediamine also induced a 50% inhibition of TX1 cell peroxidase activity. Diethyldithiocarbamate in a concentration range between 25 and 500 microM directly inhibited peroxidase activity in TX1 cell homogenates in a concentration-dependent manner. Similar results were observed with purified horseradish peroxidase. The kinetics of peroxidase activity were studied in homogenates from control cells and cells treated with 750 microM and 25 mM diethyldithiocarbamate. There was no significant difference among the Km values among the three groups with a mean (+/- standard error) Km of 2.58 +/- 0.23 mM. However, the Vmax differed from 4.02 to 2.12 nmoles tetraguaiacol/min/micrograms protein, in the control and in the 25 mM diethyldithiocarbamate treatment group, respectively. These data indicate that diethyldithiocarbamate is a non-competitive inhibitor of TX1 cell peroxidase.
Plewa
M J
MJ
Institute for Environmental Studies, University of Illinois, Urbana-Champaign 61801.
Smith
S R
SR
Wagner
E D
ED
D001711:Biotransformation; D002455:Cell Division; D002460:Cell Line; D004050:Ditiocarb / Q000494:pharmacology*; D005449:Fluorenes / Q000378:metabolism* / Q000633:toxicity; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors; D007700:Kinetics; D009153:Mutagens; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D010655:Phenylenediamines / Q000378:metabolism* / Q000633:toxicity; D010947:Plants, Toxic; D014026:Nicotiana / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D005449:Fluorenes; D009153:Mutagens; D010655:Phenylenediamines; C012177:2-aminofluorene; D004050:Ditiocarb; D006735:Horseradish Peroxidase; D010544:Peroxidases; C008381:3-phenylenediamine