Vanderlaan M, Watkins B E, Hwang M, Knize M G, Felton J S
Biomedical Sciences Division, Lawerence Livermore National Laboratory, Livermore, CA 94550.
Carcinogenesis. 1988 Jan;9(1):153-60. doi: 10.1093/carcin/9.1.153.
A family of 2-amino-N-methylimidazoazaarene (AIA) mutagens are produced in meats by cooking, and are of concern as potential carcinogens in the human diet. These are potent genotoxins in bacterial mutation assays, but are present only in trace quantities in cooked foods. Conventional analytical chemistry methods have allowed us to identify six members of the AIA class, but these methods are much too labor-intensive for us to quantify mutagens in large numbers of meat samples. To improve the assay of these mutagens we have developed six monoclonal antibodies (named IQ-1, IQ-2, AIA-1, AIA-2, AIA-4, and AIA-7) and demonstrated their utility in an immunoassay for cooked food mutagens. Each antibody has its own unique binding selectivity pattern; some are compound-specific, and some class-specific. A comparison was made between cooked beef extracts that differed 200-fold in mutagenic activity. The high-mutagen extract had significantly more material that was immunologically cross-reactive with the anti-AIA antibodies than did the low-mutagen extract. Taken as a set, these antibodies will allow rapid quantitation of foods for several AIA mutagens, and will aid in the isolation and characterization of other AIAs and AIA-metabolites.
一类2-氨基-N-甲基咪唑并氮杂芳烃(AIA)诱变剂在肉类烹饪过程中产生,作为人类饮食中的潜在致癌物受到关注。这些物质在细菌突变试验中是强效基因毒素,但在熟食中仅以痕量存在。传统分析化学方法已使我们能够鉴定出AIA类的六个成员,但这些方法过于耗费人力,以至于我们无法对大量肉类样品中的诱变剂进行定量。为改进这些诱变剂的检测方法,我们开发了六种单克隆抗体(命名为IQ-1、IQ-2、AIA-1、AIA-2、AIA-4和AIA-7),并证明了它们在熟食诱变剂免疫测定中的实用性。每种抗体都有其独特的结合选择性模式;有些是化合物特异性的,有些是类别特异性的。对诱变活性相差200倍的熟牛肉提取物进行了比较。高诱变活性提取物中与抗AIA抗体发生免疫交叉反应的物质比低诱变活性提取物中的显著更多。总体而言,这些抗体将能够快速定量多种AIA诱变剂的食物,并有助于分离和鉴定其他AIA及其代谢产物。