Malaveille C, Hautefeuille A, Brun G, Vineis P, Bartsch H
International Agency for Research on Cancer, Lyon, France.
Carcinogenesis. 1992 Dec;13(12):2317-20. doi: 10.1093/carcin/13.12.2317.
Extracts of human urine were shown to contain substances that strongly inhibited the liver S9-mediated mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Salmonella typhimurium TA98 strain in a liquid incubation assay. The inhibitory effect was unrelated to cytotoxicity and was similar with urine extracts from smokers and non-smokers. Under similar assay conditions, the mutagenicity of the related amino-imidazoazaarenes, 2-amino-3-methyl-imidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was also found to be strongly inhibited by urine extracts. Decreased or enhanced mutagenicity was seen with 2-acetyl-aminofluorene and 2-aminoanthracene depending on the type of assay, and the time of incubation in liquid medium. A weak inhibition of the mutagenicity of 2-nitrofluorene, a direct-acting mutagen, was observed only after a short incubation time. Mutagenicity of 4-nitroquinoline N-oxide was not altered by the presence of urine extracts at concentrations shown to be inhibitory for the mutagenicity of heterocyclic aromatic amines. Our data suggest that the inhibitory substances in urine act through their capacity to non covalently bind the parent heterocyclic and aromatic amines, thus affecting their availability in aqueous medium for diffusion into liver microsomes where metabolic activation takes place.
在液体培养试验中，人尿提取物被证明含有能强烈抑制鼠伤寒沙门氏菌TA98菌株中2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）的肝脏S9介导的致突变性的物质。这种抑制作用与细胞毒性无关，并且吸烟者和非吸烟者的尿提取物的抑制作用相似。在类似的试验条件下，还发现相关的氨基咪唑氮杂芳烃，2-氨基-3-甲基咪唑并[4,5-f]喹啉、2-氨基-3,8-二甲基咪唑并[4,5-f]喹啉和2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉的致突变性也被尿提取物强烈抑制。根据试验类型和在液体培养基中的孵育时间，2-乙酰氨基芴和2-氨基蒽的致突变性出现降低或增强。仅在短时间孵育后，观察到对直接作用的诱变剂2-硝基芴的致突变性有微弱抑制。在对杂环芳香胺的致突变性有抑制作用的浓度下，尿提取物的存在并未改变4-硝基喹啉N-氧化物的致突变性。我们的数据表明，尿中的抑制物质通过其与母体杂环和芳香胺非共价结合的能力起作用，从而影响它们在水性介质中扩散到发生代谢活化的肝脏微粒体中的可用性。
