Characterization of 4-nitro-o-phenylenediamine activation by plant systems.
4-Nitro-o-phenylenediamine (NOP) is a powerful direct-acting mutagen which demonstrates significant enhancement in mutagenicity when exposed to plant enzymatic systems. Evidence implicating the involvement of peroxidactic oxidation in NOP activation has been obtained from plant-cell suspension and isolated enzyme experiments. Using selected cytochrome P450 and peroxidase enzyme inhibitors in conjunction with Salmonella typhimurium strain TA98 and intact plant-cell activating systems as well as isolated horseradish peroxidase enzyme we have further investigated NOP activation by plant systems. The activation of NOP by both plant cells and by horseradish peroxidase was suppressed by the P450 inhibitors methimazole and (+)-catechin and by the peroxidase inhibitors diethyldithiocarbamate and potassium cyanide, but was not suppressed by the P450 inhibitors metyrapone and 7,8-benzoflavone. In addition, peroxidase enzymatic activity was measured and found to be inhibited by methimazole, diethyldithiocarbamate and potassium cyanide but not by (+)-catechin. The data strongly support the involvement of exogenous peroxidase in the plant activation of NOP, but point to a complex metabolic system that requires multistep processing before full mutagenic potential of the plant-activated component of NOP is expressed.
Wilson
L
L
Biology Department, Hope College, Holland, MI 49423.
Williamson
T
T
Gronowski
J
J
Gentile
G J
GJ
Gentile
J M
JM
D000704:Analysis of Variance; D001711:Biotransformation; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D010655:Phenylenediamines / Q000378:metabolism* / Q000633:toxicity; D010947:Plants, Toxic; D014026:Nicotiana / Q000166:cytology / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D009153:Mutagens; D010655:Phenylenediamines; C012277:1,2-diamino-4-nitrobenzene; D003577:Cytochrome P-450 Enzyme System; D006735:Horseradish Peroxidase