Felton J S, Knize M G, Shen N H, Lewis P R, Andresen B D, Happe J, Hatch F T
Carcinogenesis. 1986 Jul;7(7):1081-6. doi: 10.1093/carcin/7.7.1081.
A new mutagenic compound has been isolated from ground beef which was fried at 300 degrees C for 5.5 min on each side. The new mutagen was purified using an aqueous acid extraction, XAD-2 adsorption-solvent elution, a series of preparative and analytical h.p.l.c. purification steps, and monitored with the Ames/Salmonella assay. This study reveals a new mutagen member of the amino-imidazoazaarene class of aromatic amines, having a mol. w of 224, and a formula of C13H12N4 as determined by high-resolution mass spectrometry. N.m.r. spectrometry supports the structure, 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), for the new mutagen. The 1-methyl and 3-methyl synthesized isomers of PhIP were compared to the purified mutagen. The two isomers had identical mass spectra to the purified compound, but only the 1-methyl isomer showed similar u.v. and n.m.r. spectra. The two synthetic isomers were separable by h.p.l.c. and the beef derived component co-eluted with the 1-methyl-PhIP isomer. PhIP has a specific activity in the Ames/Salmonella assay of 1950 revertants/microgram. Although it is not as mutagenic as other compounds isolated from fried beef (e.g. MeIQx, 58 000 revertants/microgram) it is the most abundant mutagenic compound by mass in fried beef. PhIP is present at approximately 15 p.p.b. of the original weight of uncooked beef (accounting for 75% of the mass of genotoxic material) and contributes 18% of the total mutagenicity of the fried beef.
从每面在300摄氏度下煎5.5分钟的碎牛肉中分离出一种新的诱变化合物。使用酸水萃取、XAD - 2吸附 - 溶剂洗脱、一系列制备和分析高效液相色谱纯化步骤对新诱变剂进行纯化，并通过艾姆斯/沙门氏菌试验进行监测。本研究揭示了一种新的诱变剂，属于氨基 - 咪唑氮杂芳烃类芳香胺，通过高分辨率质谱测定其分子量为224，分子式为C₁₃H₁₂N₄。核磁共振光谱支持该新诱变剂的结构为2 - 氨基 - 1 - 甲基 - 6 - 苯基 - 咪唑[4,5 - b]吡啶（PhIP）。将PhIP的1 - 甲基和3 - 甲基合成异构体与纯化的诱变剂进行比较。这两种异构体的质谱与纯化化合物相同，但只有1 - 甲基异构体显示出相似的紫外和核磁共振光谱。这两种合成异构体可通过高效液相色谱分离，且牛肉衍生成分与1 - 甲基 - PhIP异构体共洗脱。PhIP在艾姆斯/沙门氏菌试验中的比活性为1950回复突变体/微克。虽然它不像从煎牛肉中分离出的其他化合物那样具有强诱变作用（例如MeIQx，58000回复突变体/微克），但按质量计它是煎牛肉中最丰富的诱变化合物。PhIP在未煮牛肉原始重量中约占15 ppm（占遗传毒性物质质量的75%），并占煎牛肉总诱变性的18%。
