Sugimura T, Wakabayashi K, Ohgaki H, Takayama S, Nagao M, Esumi H
National Cancer Center Research Institute, Tokyo, Japan.
Princess Takamatsu Symp. 1990;21:279-88.
Humans are continuously exposed to naturally occurring and industrial xenobiotics in their daily lives. Heterocyclic amines, which are formed during the cooking of proteinaceous foods, have been categorized as a new class of naturally occurring xenobiotics. They are divided into 2-amino-3-methylimidazo[4,5-f] quinoline (IQ)- and non-IQ-types. The amounts and proportion of total mutagenicity contributed by the IQ-type heterocyclic amines in cooked food are greater than those of the non-IQ-types. Precursors of the IQ-type heterocyclic amines including IQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are creatinine, amino acids and sugars in meat and fish. Both types of heterocyclic amines are carcinogenic in mice and rats. All heterocyclic amines except PhIP frequently induce cancers in the liver, while PhIP induces lymphomas in mice and carcinomas of the colon and mammary gland in rats. Based on quantitative analysis of heterocyclic amines in cooked food and levels of excretion of unchanged heterocyclic amines in human urine, total heterocyclic amine intake was calculated to be around 0.4-16 micrograms/person per day. As in the case of other naturally occurring xenobiotics, and degree of exposure is small and is presumably insufficient alone to account for the development of human cancer. Nevertheless, a linear relationship has been demonstrated between DNA adduct levels and a wide range of doses of MeIQx in animals. In addition, combined treatment with five heterocyclic amines yielded additive or synergistic effects in the development of glutathione S-transferase placental form (GST-P) positive foci. Taking these results and current observations of multiple genetic alterations in human cancers into consideration together, heterocyclic amines are probably involved in the development of human cancer in the presence of other carcinogens, tumor promoters and factors stimulating cancer progression.
人类在日常生活中持续接触天然存在的和工业来源的外源性物质。在蛋白质类食物烹饪过程中形成的杂环胺，已被归类为一类新的天然存在的外源性物质。它们分为2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ）型和非IQ型。烹饪食物中IQ型杂环胺对总致突变性的贡献量和比例大于非IQ型。IQ型杂环胺的前体包括IQ、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），存在于肉类和鱼类中的肌酐、氨基酸和糖类中。这两种类型的杂环胺在小鼠和大鼠中都具有致癌性。除PhIP外，所有杂环胺都经常诱发肝脏癌症，而PhIP在小鼠中诱发淋巴瘤，在大鼠中诱发结肠癌和乳腺癌。根据对烹饪食物中杂环胺的定量分析以及人体尿液中未变化的杂环胺排泄水平，计算出杂环胺的总摄入量约为每人每天0.4 - 16微克。与其他天然存在的外源性物质情况一样，接触程度较小，单独而言可能不足以导致人类癌症的发生。然而，在动物中已证明DNA加合物水平与多种剂量的MeIQx之间存在线性关系。此外，五种杂环胺联合处理在谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶的形成中产生相加或协同作用。综合考虑这些结果以及目前对人类癌症中多种基因改变的观察，杂环胺可能在存在其他致癌物、肿瘤促进剂和刺激癌症进展的因素时参与人类癌症的发生。
