Yamazoe Y, Ishii K, Kamataki T, Kato R, Sugimura T
Chem Biol Interact. 1980 May;30(2):125-38. doi: 10.1016/0009-2797(80)90120-9.
The mutagenic compound derived from the pyrolysis of tryptophan, 3-amino-1-methyl-5H-pyrido-[4,3b]indole (Trp-P-2) was metabolized by rat liver microsomes to more than four metabolites, separable by high performance liquid chromatography. Among these metabolites, two metabolites, M-3 and M-4 were directly active in increasing the frequency of mutation in Salmonella typhimurium TA98. Treatments of rats with polychlorinated biphenyl (PCB) or 3-methylcholanthrene dramatically induced the activity of liver microsomes to form these active metabolites, while treatment with phenobarbital was without effect. A major active metabolite (M-3) formed the pentacyano-ammine ferroate, which is known to be formed by reaction of sodium pentacyano-ammine ferroate with some hydroxylamines. Further this metabolite was oxidized to the minor active metabolite (M-4) with potassium ferricyanide or gamma-manganese dioxide, and was reduced back to Trp-P-2 with titanium trichloride. These results indicated that the major active metabolite of Trp-P-2, which is formed by cytochrome P-450, is the 3-hydroxyamino derivative.
色氨酸热解产生的诱变化合物3-氨基-1-甲基-5H-吡啶并-[4,3b]吲哚（Trp-P-2）被大鼠肝脏微粒体代谢为四种以上的代谢产物，这些代谢产物可用高效液相色谱法分离。在这些代谢产物中，两种代谢产物M-3和M-4直接具有增加鼠伤寒沙门氏菌TA98突变频率的活性。用多氯联苯（PCB）或3-甲基胆蒽处理大鼠可显著诱导肝脏微粒体形成这些活性代谢产物的活性，而用苯巴比妥处理则无效。一种主要的活性代谢产物（M-3）形成了五氰合氨合亚铁酸盐，已知五氰合氨合亚铁酸钠与某些羟胺反应会形成这种物质。此外，该代谢产物用铁氰化钾或γ-二氧化锰氧化可生成次要的活性代谢产物（M-4），用三氯化钛可将其还原回Trp-P-2。这些结果表明，由细胞色素P-450形成的Trp-P-2的主要活性代谢产物是3-羟基氨基衍生物。
