Abteilung Neuropathologie, Pathologisches Institut der Universität Freiburg, 78 Freiburg, GFR.
Carcinogenesis. 1980 Jan;1(1):111-3. doi: 10.1093/carcin/1.1.111.
Methylated purines were determined in DNA of various gerbil tissues following a single i.v. injection of N-[14C]methyl-N-nitrosourea (10 mg/kg). Enzymic removal of the promutagenic base O6-methylguanine was most efficient in the liver, followed by kidney, lung and brain. In cerebral DNA, 40% of the initial concentration was still present after 6 months. Since the gerbil brain is apparently not susceptible to the oncogenic effect of methylnitrosourea and related carcinogens, these data indicate that the formation and persistence of O6-alkylguanine may constitute a necessary although not sufficient event for the initiation of organ-specific carcinogenesis by monofunctional alkylating agents.
在单次静脉注射 N-[14C]甲基-N-亚硝脲(10mg/kg)后,测定了各种沙鼠组织的 DNA 中的甲基嘌呤。在肝脏中,酶促去除诱变碱基 O6-甲基鸟嘌呤的效率最高,其次是肾脏、肺和大脑。在脑 DNA 中,初始浓度的 40%在 6 个月后仍存在。由于沙鼠大脑显然不易受到甲基亚硝脲和相关致癌剂的致癌作用的影响,这些数据表明,O6-烷基鸟嘌呤的形成和持续存在可能构成单功能烷化剂引发器官特异性致癌作用的必要但非充分事件。