Age-dependent increases of DNA adducts (I-compounds) in human and rat brain DNA

Mutation Research/DNAging Pub Date : 1993-01-01 DOI:10.1016/0921-8734(93)90007-P

Kurt Randerath , Kim L. Putman , Heinz H. Osterburg , Steven A. Johnson , David G. Morgan , Caleb E. Finch

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引用次数: 58

Abstract

Brain DNA from 20 humans ranging in age from neonatal to 100 years was analyzed by the nuclease P1-enhanced version of the ³²P-postlabeling assay for bulky covalently modified nucleotides. A reproducible pattern of three ³²P-labeled spots was obtained by thin-layer chromatography followed by autoradiography. Two of these spots increased with age (Mann-Whitney U-test; P<0.001; comparison of ages ≤ 60 years and ages > 60 years). Thus, these spots met the definition of I-compounds. Rat brain DNA exhibited the same two I-spots, whose intensities also increased with animal age (1, 4, and 10 months). In humans, considerable individual variation of brain I-compound levels was observed, especially at ages > 60 years, presumably reflecting environmental, life-style, or genetic factors. This variation was not noted for brain DNA of laboratory rats. Thus, human brain DNA undergoes progressive covalent modifications with aging.

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人类和大鼠脑DNA中DNA加合物(i -化合物)的年龄依赖性增加

用核酸酶p1增强版的32p标记后测定法分析了20名年龄从新生儿到100岁不等的人的脑DNA。通过薄层色谱和放射自显影获得了三个32p标记点的可重复模式。其中两个斑点随着年龄的增长而增加(Mann-Whitney U-test;术中,0.001;年龄≤60岁与年龄>60年)。因此，这些点符合i类化合物的定义。大鼠脑DNA呈现相同的两个i点，其强度也随着动物年龄(1、4、10个月)的增加而增加。在人类中，观察到相当大的脑i -化合物水平的个体差异，特别是在年龄和gt;60岁，大概反映了环境、生活方式或遗传因素。在实验室大鼠的大脑DNA中没有发现这种变异。因此，随着年龄的增长，人类大脑DNA经历了渐进的共价修饰。

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Mutation Research/DNAging

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