CHARACTERIZATION OF 4-NITRO-O-PHENYLENEDIAMINE ACTIVATION BY PLANT-SYSTEMS

4-Nitro-o-phenylenediamine (NOP) is a powerful direct-acting mutagen w hich demonstrates significant enhancement in mutagenicity when exposed to plant enzymatic systems. Evidence implicating the involvement of p eroxidactic oxidation in NOP activation has been obtained from plant-c ell suspension and isolated enzyme experiments. Using selected cytochr ome P450 and peroxidase enzyme inhibitors in conjunction with Salmonel la typhimurium strain TA98 and intact plant-cell activating systems as well as isolated horseradish peroxidase enzyme we have further invest igated NOP activation by plant systems. The activation of NOP by both plant cells and by horseradish peroxidase was suppressed by the P450 i nhibitors methimazole and (+)-catechin and by the peroxidase inhibitor s 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 b y 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 meta bolic system that requires multistep processing before full mutagenic potential of the plant-activated component of NOP is expressed.