Wilson L, Williamson T, Gronowski J, Gentile G J, Gentile J M
Biology Department, Hope College, Holland, MI 49423.
Mutat Res. 1994 May 1;307(1):185-92. doi: 10.1016/0027-5107(94)90291-7.
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.
4-硝基邻苯二胺（NOP）是一种强效的直接作用诱变剂，当暴露于植物酶系统时，其诱变性会显著增强。从植物细胞悬浮液和分离酶实验中已获得涉及过氧化物酶促氧化参与NOP活化的证据。我们使用选定的细胞色素P450和过氧化物酶抑制剂，结合鼠伤寒沙门氏菌TA98菌株和完整的植物细胞活化系统以及分离的辣根过氧化物酶，进一步研究了植物系统对NOP的活化作用。甲巯咪唑和（+）-儿茶素这两种细胞色素P450抑制剂以及二乙基二硫代氨基甲酸盐和氰化钾这两种过氧化物酶抑制剂抑制了植物细胞和辣根过氧化物酶对NOP的活化，但美替拉酮和7,8-苯并黄酮这两种细胞色素P450抑制剂没有抑制作用。此外，还测定了过氧化物酶的酶活性，发现其受到甲巯咪唑、二乙基二硫代氨基甲酸盐和氰化钾的抑制，但不受（+）-儿茶素的抑制。这些数据有力地支持了外源性过氧化物酶参与植物对NOP的活化，但也表明存在一个复杂的代谢系统，在NOP的植物活化成分充分发挥诱变潜力之前需要多步处理。
