COMPARISON OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY BASED ON CELLULAR DNA CONTENT IN HUMAN, RAT AND MOUSE-TISSUES
COMPARISON OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY BASED ON CELLULAR DNA CONTENT IN HUMAN, RAT AND MOUSE-TISSUES
复制标题
DOI：
10.1093/carcin/7.5.745
复制
发表时间：
1986-05-01
期刊：
影响因子：
4.7
通讯作者：
BERGER, NA
中科院分区：
文献类型：
--
作者：
GERSON, SL;TREY, JE;BERGER, NA
O 6-烷基鸟嘌呤-DNA烷基转移酶（烷基转移酶）是O 6-烷基鸟嘌呤的修复蛋白，O 6-烷基鸟嘌呤是由多种烷化剂形成的预诱变加合物。以前比较的修复能力的O 6-烷基鸟嘌呤在不同的组织中表示的烷基转移酶活性相对于总蛋白质，并断言，组织与低水平的活动是在更大的风险比组织具有较高的活性水平的致突变性损伤。因为烷基转移酶使用DNA作为底物，并且因为组织在蛋白质含量方面差异很大，所以组织烷基转移酶活性的比较可能更适当地基于细胞DNA含量。我们比较了烷基转移酶活性相对于组织DNA含量与活性相关的蛋白质含量在人类，大鼠和小鼠组织。在每个物种中，肝脏含有最高水平的活动，使用任何一种方法。与其他人的发现一致，在人脑、大鼠脑和小肠以及小鼠肾脏中观察到相对于蛋白质的低水平烷基转移酶活性。然而，基于相对于DNA含量的烷基转移酶活性，在人骨髓髓样前体、大鼠骨髓、脑和肠以及小鼠脾脏和骨髓中观察到低水平的活性。组织间的活性范围在人体中为18倍，在大鼠中为15倍，在小鼠中为8倍。一般而言，每个组织的烷基转移酶活性相对于DNA的排序为人>大鼠>小鼠。这些结果表明，小鼠比大鼠或人对亚硝基脲更敏感。在每个物种中，相对于组织DNA含量具有低水平烷基转移酶活性的器官似乎是亚硝基脲暴露后致突变损伤的靶点。
O6-Alkylguanine-DNA alkyltransferase (alkyltransferase) is the repair protein for O6-alkylguanine, a pre-mutagenic adduct formed by a variety of alkylating agents. Previous comparisons of the repair capacity of O6-alkylguanine in different tissues have expressed the alkyltransferase activity relative to total protien, and have asserted that tissues with low levels of activity were at greater risk for mutagenic damage than tissues with higher levels of activity. Because the alkyltransferase used DNA as substrate, and because tissue vary greatly in protein content, comparisons of tissue alkyltransferase activity may be more appropriately based on cellular DNA content. We compared alkyltransferase activity relative to tissue DNA content with the activity related to protein content in human, rat and mouse tissues. In each species, liver containing the highest level of activity using either method. In agreement with the findings of others, low levels of alkyltransferase activity relative to protein were seen in human brain, rat brain and small intestine, and mouse kidney. However, based on alkyltransferase activity relative to DNA content, low levels of activity were seen in human bone marrow myeloid precursors, rat bone marrow, brain and intestine, and mouse spleen and bone marrow. The range of activity between tissue was 18-fold in human, 15-fold in rat and 8-fold in mouse. In general, the rank of alkyltransferase activity relative to DNA for each tissue was human > rat > mouse. These results suggest that the mouse is more susceptible to nitrosoureas than rat or human. In each species, the organs with low levels of alkyltransferase activity relative to tissue DNA content would appear to be targets for mutagenic damage following nitrosourea exposure.