Likhachev A Ia, Zhukovskaia N V, Anisimov V N, Hall J
Vopr Onkol. 1991;37(2):197-203.
Concentrations of O6-alkylguanine-DNA alkyltransferase (AT) which repairs a procarcinogenic DNA adduct O6-alkylguanine formed following exposure to carcinogenic N-nitroso compounds were measured in the liver, kidney and peripheral blood leukocytes of male L10 rats aged 1, 4, 14, 22 and 36 months. In the liver, peak AT level was observed at the age of 14 and 22 months. No age-related differences were established for kidney and leukocytes. The highest concentration of AT was registered in the kidney while the lowest--in leukocytes. The study revealed stoichiometric transfer of O6-methylguanine methyl group to cysteine residue of AT. No positive correlation was established between individual tissue AT levels in different animals. The highest level of total protein and the lowest concentration of DNA were observed in the liver and kidney of 14-22 month-old rats. The data obtained provide an explanation for relative resistance of 1-2 year-old rats to hepatotropic nitrosamine and suggest that the level of AT in a given tissue is not predictive of its activity in other tissues.
在1、4、14、22和36月龄的雄性L10大鼠的肝脏、肾脏和外周血白细胞中,检测了O6-烷基鸟嘌呤-DNA烷基转移酶(AT)的浓度,该酶可修复暴露于致癌性N-亚硝基化合物后形成的致癌DNA加合物O6-烷基鸟嘌呤。在肝脏中,14和22月龄时观察到AT水平峰值。肾脏和白细胞未发现与年龄相关的差异。AT浓度在肾脏中最高,而在白细胞中最低。该研究揭示了O6-甲基鸟嘌呤甲基基团向AT半胱氨酸残基的化学计量转移。不同动物个体组织AT水平之间未发现正相关。在14-22月龄大鼠的肝脏和肾脏中观察到最高水平的总蛋白和最低浓度的DNA。所获得的数据解释了1-2岁大鼠对亲肝亚硝胺的相对抗性,并表明给定组织中AT的水平不能预测其在其他组织中的活性。