Frandsen H, Damkjaer S, Grivas S, Andersson R, Binderup M L, Larsen J C
Institute of Toxicology, National Food Agency, Søborg, Denmark.
Mutagenesis. 1998 Mar;13(2):181-5. doi: 10.1093/mutage/13.2.181.
2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a mutagenic and carcinogenic heterocyclic amine formed as a pyrolysis product during cooking of food and combustion of tobacco. Hepatic microsomes from PCB-induced rats metabolized MeA alpha C to four products, of which three were non-mutagenic and one was mutagenic without S9 activation. The three non-mutagenic products, which accounted for 83% of the metabolism of MeA alpha C, were characterized by mass spectrometry and NMR spectroscopy as 6-hydroxy-MeA alpha C, 7-hydroxy-MeA alpha C and 3-hydroxy-methyl-A alpha C. The mutagenic metabolite, accounting for 17% of the metabolism of MeA alpha C, was characterized as N2-hydroxy-MeA alpha C by comparison with the HPLC retention time and UV spectrum of N2-hydroxy-MeA alpha C obtained by chemical synthesis. N2-Hydroxy-MeA alpha C was very reactive and a part of it bound covalently to microsomal proteins during incubation and a part was degraded to other products during incubation or chromatography. N2-Hydroxy-MeA alpha C was mutagenic in Salmonella typhimurium TA98 without metabolic activation, resulting in 5070 revertants/microgram, which was > 20 times the specific mutagenic activity of the parent compound.
2-氨基-3-甲基-9H-吡啶并[2,3-b]吲哚（MeAαC）是一种诱变和致癌的杂环胺，在食物烹饪和烟草燃烧过程中作为热解产物形成。来自多氯联苯诱导大鼠的肝微粒体将MeAαC代谢为四种产物，其中三种无诱变活性，一种在无S9激活的情况下具有诱变活性。占MeAαC代谢83%的三种无诱变活性产物，通过质谱和核磁共振光谱鉴定为6-羟基-MeAαC、7-羟基-MeAαC和3-羟基甲基-AαC。通过与化学合成得到的N2-羟基-MeAαC的高效液相色谱保留时间和紫外光谱进行比较，将占MeAαC代谢17%的诱变代谢物鉴定为N2-羟基-MeAαC。N2-羟基-MeAαC非常活泼，在孵育过程中一部分与微粒体蛋白共价结合，一部分在孵育或色谱过程中降解为其他产物。N2-羟基-MeAαC在无代谢激活的情况下对鼠伤寒沙门氏菌TA98具有诱变活性，产生5070个回复突变体/微克，这是母体化合物比诱变活性的20倍以上。
