Gerson S L, Trey J E, Miller K, Berger N A
Carcinogenesis. 1986 May;7(5):745-9. doi: 10.1093/carcin/7.5.745.
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 protein, 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 uses DNA as substrate, and because tissues 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 tissues 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 greater than rat greater than 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.
O6-烷基鸟嘌呤-DNA烷基转移酶（烷基转移酶）是一种修复蛋白，负责修复O6-烷基鸟嘌呤，这是一种由多种烷化剂形成的前诱变加合物。先前对不同组织中O6-烷基鸟嘌呤修复能力的比较，是相对于总蛋白来表达烷基转移酶活性的，并断言活性水平低的组织比活性水平高的组织面临更大的诱变损伤风险。由于烷基转移酶以DNA为底物，且各组织的蛋白质含量差异很大，因此基于细胞DNA含量来比较组织烷基转移酶活性可能更为合适。我们比较了人、大鼠和小鼠组织中相对于组织DNA含量的烷基转移酶活性与相对于蛋白质含量的活性。在每个物种中，无论采用哪种方法，肝脏的活性水平最高。与其他人的研究结果一致，在人脑、大鼠脑、小肠和小鼠肾脏中，相对于蛋白质的烷基转移酶活性水平较低。然而，基于相对于DNA含量的烷基转移酶活性，在人骨髓髓系前体细胞、大鼠骨髓、脑和小肠以及小鼠脾脏和骨髓中观察到活性水平较低。不同组织之间的活性范围在人中为18倍，在大鼠中为15倍，在小鼠中为8倍。一般来说，各组织相对于DNA的烷基转移酶活性排名为人＞大鼠＞小鼠。这些结果表明，小鼠比大鼠或人更容易受到亚硝基脲的影响。在每个物种中，相对于组织DNA含量而言烷基转移酶活性水平较低的器官，似乎是亚硝基脲暴露后诱变损伤的靶器官。
