Alexander J, Reistad R, Hegstad S, Frandsen H, Ingebrigtsen K, Paulsen J E, Becher G
Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403, Oslo, Norway.
Food Chem Toxicol. 2002 Aug;40(8):1131-7. doi: 10.1016/s0278-6915(02)00053-4.
Various methods of exposure assessment, such as questionnaires, sometimes combined with pictures of cooked meat, have been employed in investigations on the relationship between heterocyclic amines (HA) and health effects. However, as the content of heterocyclic amines vary greatly with cooking conditions, it is difficult to obtain an accurate estimate of the exposure. To improve the exposure assessment, the use of biomarkers has been investigated. The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is well characterised. In humans, the major part of the dose is excreted in urine within 24-48 h following a meal. A few percent is excreted as parent compounds, whereas the major part is metabolites. Urinary level of parent HA reflects only recent exposure. However, the pattern of excreted metabolites might indicate the capacity to activate or detoxify HAs. The excretion of glucuronide conjugates of N-hydroxy-PhIP and N-hydroxy-MeIQx could be a marker for the N-hydroxylation capacity and the dose of the proximate metabolites. Recently, we proposed 5-OH-PhIP as a marker for the ultimate reactive metabolite of PhIP, since it is formed from this compound as a by-product along with the formation of PhIP-DNA adducts. In a search for biomarkers reflecting exposure over some time, blood protein adducts with a longer lifespan have been investigated, and PhIP adducts of serum albumin and haemoglobin from meat-consuming humans were recently reported. Many compounds, like drugs, nicotine and narcotics, bind to melanin in hair and give information on exposure for longer time periods. In mice, PhIP is irreversibly incorporated in a dose-dependent manner into hair, and in humans exposed to an ordinary diet, it was found to vary from <50 to 5000 pg PhIP/g hair. The incorporation is also dependent on the content of eumelanin. The use of PhIP in hair as a biomarker of exposure is promising, but needs validation, using other methods of exposure assessment.
在关于杂环胺（HA）与健康影响之间关系的调查中，已经采用了各种暴露评估方法，如问卷调查，有时还会结合熟肉的图片。然而，由于杂环胺的含量会因烹饪条件而有很大差异，因此很难准确估计暴露量。为了改进暴露评估，人们对生物标志物的使用进行了研究。2-氨基-3,8-二甲基咪唑[4,5-f]喹喔啉（MeIQx）和2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）的代谢过程已得到充分表征。在人类中，大部分剂量在进食后24至48小时内通过尿液排出。只有百分之几以母体化合物的形式排出，而大部分是代谢产物。母体HA的尿液水平仅反映近期暴露情况。然而，排出的代谢产物模式可能表明激活或解毒HA的能力。N-羟基-PhIP和N-羟基-MeIQx的葡萄糖醛酸共轭物的排泄可能是N-羟基化能力和近端代谢产物剂量的标志物。最近，我们提出5-OH-PhIP作为PhIP最终活性代谢产物的标志物，因为它是在形成PhIP-DNA加合物的同时作为该化合物的副产物形成的。在寻找反映一段时间内暴露情况的生物标志物的过程中，人们对寿命更长的血液蛋白加合物进行了研究，最近有报道称在食用肉类的人群中发现了血清白蛋白和血红蛋白的PhIP加合物。许多化合物，如药物、尼古丁和麻醉品，会与头发中的黑色素结合，并提供更长时间段内的暴露信息。在小鼠中，PhIP以剂量依赖的方式不可逆地掺入毛发中，在食用普通饮食的人类中，发现其含量在<50至5000 pg PhIP/克头发之间变化。这种掺入还取决于真黑素的含量。将毛发中的PhIP用作暴露生物标志物很有前景，但需要使用其他暴露评估方法进行验证。
