Turesky R J, Markovic J
Nestec Ltd., Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
Carcinogenesis. 1995 Sep;16(9):2275-9. doi: 10.1093/carcin/16.9.2275.
DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) have been measured in the liver, kidney, and colo-rectum of male Fischer-344 rats given a single oral dose of IQ (20 mg/kg). The pattern and distribution of DNA adducts examined by 32P-postlabeling was similar in all tissues. N-(Deoxyguanosin-8-yl)-2-amino-3-methylimidazo-[4,5-f]quinoline (dG-C8-IQ) was the principal adduct identified and it accounted for approximately 50-70% of the observed radioactivity, followed by (deoxyguanosin-N2-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N2-IQ) which accounted for 15-20% of the radioactivity. Twenty-four hours after IQ treatment, DNA modification was greatest in the liver at a level of 7.64 +/- 1.08 adducts per 10(7) bases, followed by kidney at 2.04 +/- 0.32 adducts per 10(7) bases, and colorectum at 1.08+/-0.22 adducts per 10(7) bases. Liver and colo-rectum are target tissues of tumorigenesis in the rat during chronic feeding studies with IQ; however, tumors are not formed in the kidney. Therefore, factors in addition to IQ-guanine adduct formation, such as adduct persistence, error-prone repair, and tumor promotion must contribute to organ susceptibility of IQ-induced carcinogenesis.
给雄性Fischer - 344大鼠单次口服剂量为20mg/kg的2 - 氨基 - 3 - 甲基咪唑[4,5 - f]喹啉(IQ)后,已对其肝脏、肾脏和结肠直肠中的IQ的DNA加合物进行了测量。通过³²P后标记法检测的DNA加合物的模式和分布在所有组织中相似。N - (脱氧鸟苷 - 8 - 基)-2 - 氨基 - 3 - 甲基咪唑[4,5 - f]喹啉(dG - C8 - IQ)是鉴定出的主要加合物,它占观察到的放射性的约50 - 70%,其次是(脱氧鸟苷 - N2 - 基)-2 - 氨基 - 3 - 甲基咪唑[4,5 - f]喹啉(dG - N2 - IQ),其占放射性的15 - 20%。IQ处理后24小时,肝脏中的DNA修饰最大,水平为每10⁷个碱基有7.64±1.08个加合物,其次是肾脏,每10⁷个碱基有2.04±0.32个加合物,结肠直肠为每10⁷个碱基有1.08±0.22个加合物。在对IQ进行慢性喂养研究期间,肝脏和结肠直肠是大鼠肿瘤发生的靶组织;然而,肾脏中不形成肿瘤。因此,除了IQ - 鸟嘌呤加合物形成之外的因素,如加合物持久性、易错修复和肿瘤促进,必定对IQ诱导的致癌作用的器官易感性有影响。