Li D H, Wang Y M, Nath R G, Mistry S, Randerath K
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
J Nutr. 1991 Jan;121(1):65-71. doi: 10.1093/jn/121.1.65.
I(indigenous)-compounds are age-related, carcinogen adduct-like, putative indigenous DNA modifications detectable by 32P-postlabeling assay in untreated animals. To investigate the origins of these DNA derivatives, we examined the effects of dietary vitamin E, a natural antioxidant, on I-compounds of rat liver and kidney DNA. Weanling female Sprague-Dawley rats were fed Draper's diets containing 0, 100, 1000, or 10,000 mg/kg alpha-tocopheryl acetate for 6 mo. The DNA from four individual rats of each group was analyzed by a nuclease P1-enhanced version of the 32P-postlabeling assay for DNA adducts. The amount of vitamin E in the liver was measured by high performance liquid chromatography. Rats fed vitamin E-deficient diet (0 mg/kg) showed identical profiles and similar levels of I-compounds as those fed the 100 mg/kg diet. Most I-spots were significantly intensified and one tissue-specific extra spot was found in both liver and kidney DNA of rats fed the 1000 or 10,000 mg/kg vitamin E diet. However, one of the five major I-spots detected in the kidney was weaker in the 1000 and 10,000 mg/kg groups than in the 0 and 100 mg/kg groups. These results show that formation of most I-compounds was not affected by vitamin E-deficient diet, and that long-term feeding of diet containing high levels of vitamin E may cause metabolic alterations leading to an increased formation of DNA-reactive (potentially mutagenic or carcinogenic) electrophiles.
I（内源性）化合物与年龄相关，类似致癌物加合物，是未经处理的动物中通过³²P后标记分析法可检测到的假定内源性DNA修饰。为了研究这些DNA衍生物的起源，我们检测了膳食维生素E（一种天然抗氧化剂）对大鼠肝脏和肾脏DNA中I化合物的影响。将断乳雌性斯普拉格-道利大鼠喂食含0、100、1000或10000mg/kg醋酸α-生育酚的德雷珀饮食6个月。通过³²P后标记分析法的核酸酶P1增强版对每组四只大鼠的DNA进行DNA加合物分析。通过高效液相色谱法测量肝脏中的维生素E含量。喂食维生素E缺乏饮食（0mg/kg）的大鼠与喂食100mg/kg饮食的大鼠表现出相同的图谱和相似水平的I化合物。在喂食1000或10000mg/kg维生素E饮食的大鼠的肝脏和肾脏DNA中，大多数I斑点显著增强，并且发现了一个组织特异性额外斑点。然而，在肾脏中检测到的五个主要I斑点之一在1000和10000mg/kg组中比在0和100mg/kg组中更弱。这些结果表明，大多数I化合物的形成不受维生素E缺乏饮食的影响，并且长期喂食含高水平维生素E的饮食可能会导致代谢改变，从而导致DNA反应性（潜在诱变或致癌）亲电试剂的形成增加。
