人类和大鼠脑DNA中DNA加合物（I-化合物）随年龄增长而增加。

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

作者信息

Randerath K, Putman K L, Osterburg H H, Johnson S A, Morgan D G, Finch C E

机构信息

Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.

出版信息

Mutat Res. 1993 Jan;295(1):11-8. doi: 10.1016/0921-8734(93)90007-p.

DOI:10.1016/0921-8734(93)90007-p

PMID:7677925

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 < or = 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.

摘要

采用核酸酶P1增强版的³²P后标记分析法，对20名年龄从新生儿到100岁的人类大脑DNA进行了分析，以检测大分子共价修饰核苷酸。通过薄层色谱法和放射自显影获得了三种³²P标记斑点的可重复模式。其中两个斑点随年龄增加而增加（曼-惠特尼U检验；P < 0.001；年龄≤60岁和年龄>60岁的比较）。因此，这些斑点符合I类化合物的定义。大鼠脑DNA也呈现出相同的两个I类斑点，其强度也随动物年龄（1、4和10个月）增加。在人类中，观察到大脑I类化合物水平存在相当大的个体差异，尤其是在年龄>60岁时，这可能反映了环境、生活方式或遗传因素。在实验室大鼠的脑DNA中未观察到这种差异。因此，人类大脑DNA会随着衰老发生渐进性的共价修饰。