Kleihues P, Veit C, Wiessler M, Hodgson R M
Carcinogenesis. 1981;2(9):897-9. doi: 10.1093/carcin/2.9.897.
Adult female NMRI mice received a single i.p injection of N-nitroso(methyl-14C)methylbenzylamine (2.5 mg/kg body weight). Multiple weekly applications of such a dose, by this route, have previously been shown to induce lung adenomas and forestomach carcinomas in all experimental animals. After a survival time of 6 h, DNA was isolated from various tissues and analysed for methylated purines by separation of the acid hydrolysate on Sephasorb columns. Highest concentrations of 7-methylguanine and 06-methylguanine were present in hepatic DNA, followed by lung and forestomach. DNA methylation in the oesophagus was only 21% less than in forestomach. Since both tissues develop a high tumour incidence after oral administration of N-nitrosomethylbenzylamine (MBN), this observation suggests that despite their anatomical similarities the level of DNA modification required for malignant transformation differs considerably in these tissue. In the remaining organs, DNA alkylation was either considerably less (colon, glandular stomach, kidney) or not detectable (small intestine, spleen). These date indicate that following i.p. injection in mice, MBN is preferentially metabolised in a non-target organ (liver). Among the various other tissues investigated, highest levels of initial DNA methylation were present in forestomach and lung, i.e., the principal target organs of MBN for this route of application.
成年雌性NMRI小鼠经腹腔单次注射N-亚硝基（甲基-14C）甲基苄胺（2.5毫克/千克体重）。此前研究表明，通过该途径每周多次给予此剂量，会在所有实验动物中诱发肺腺瘤和前胃癌。存活6小时后，从各种组织中分离出DNA，并通过在Sephasorb柱上分离酸水解产物来分析甲基化嘌呤。肝DNA中7-甲基鸟嘌呤和O6-甲基鸟嘌呤的浓度最高，其次是肺和前胃。食管中的DNA甲基化仅比前胃低21%。由于口服N-亚硝基甲基苄胺（MBN）后这两个组织都有很高的肿瘤发生率，这一观察结果表明，尽管它们在解剖学上相似，但这些组织中恶性转化所需的DNA修饰水平差异很大。在其余器官中，DNA烷基化要么明显较少（结肠、腺胃、肾脏），要么无法检测到（小肠、脾脏）。这些数据表明，在小鼠腹腔注射后，MBN优先在非靶器官（肝脏）中代谢。在所研究的各种其他组织中，前胃和肺中初始DNA甲基化水平最高，即该给药途径下MBN的主要靶器官。
