Likhachev A, Zhukovskaya N, Anisimov V, Hall J, Napalkov N
N.N. Petrov Research Institute of Oncology, Leningrad, USSR.
IARC Sci Publ. 1991(105):407-11.
Age-related differences in the sensitivity of rats to alkylating carcinogens may be dependent on various factors, including the cellular levels of O6-alkylguanine-DNA alkyltransferase (AT). In the present study, the levels of AT were measured in protein extracts prepared from liver, kidney and peripheral white blood cells of male outbred rats aged 1, 4, 14, 22 and 36 months. The AT level (expressed as activity per milligram protein) in liver extracts was lower in rats aged 1, 4 or 36 months than in extracts prepared from rats aged 14 or 22 months. This observation of a variation in AT level with age is in agreement with our previous results. The AT levels in kidney and white blood cells did not differ significantly with age, and in all cases the AT levels were lower than those observed in the liver extracts, the kidney extracts having more AT activity than the white blood cell extracts. The total protein content of both liver and kidney tissues, calculated per gram of wet tissue, increased to a maximum at 14 months and subsequently declined, the total protein content being always higher in the liver than in the kidney. In contrast, the DNA content per gram of wet tissue was highest in young animals and subsequently declined to a minimum at 14 months. The implications of this inverse relationship to the levels of AT activity are discussed.
大鼠对烷化致癌物敏感性的年龄相关差异可能取决于多种因素，包括O6-烷基鸟嘌呤-DNA烷基转移酶（AT）的细胞水平。在本研究中，测定了1、4、14、22和36月龄雄性远交系大鼠肝脏、肾脏和外周白细胞制备的蛋白质提取物中的AT水平。1、4或36月龄大鼠肝脏提取物中的AT水平（以每毫克蛋白质的活性表示）低于14或22月龄大鼠制备的提取物。AT水平随年龄变化的这一观察结果与我们之前的结果一致。肾脏和白细胞中的AT水平在年龄上没有显著差异，并且在所有情况下，AT水平均低于肝脏提取物中的水平，肾脏提取物的AT活性高于白细胞提取物。以每克湿组织计算，肝脏和肾脏组织的总蛋白含量在14个月时增加到最大值，随后下降，肝脏中的总蛋白含量始终高于肾脏。相比之下，每克湿组织的DNA含量在幼年动物中最高，随后在14个月时下降到最低值。讨论了这种反比关系对AT活性水平的影响。
