THE PREVENTION OF THYMIC LYMPHOMAS IN TRANSGENIC MICE BY HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE
THE PREVENTION OF THYMIC LYMPHOMAS IN TRANSGENIC MICE BY HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE
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DOI：
10.1126/science.8421782
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发表时间：
1993-01-08
期刊：
影响因子：
56.9
通讯作者：
GERSON, SL
中科院分区：
文献类型：
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作者：
DUMENCO, LL;ALLAY, E;GERSON, SL
亚硝基源形成o6 -烷基鸟嘌呤- dna加合物，转化为G到A的转变，这种突变在亚硝基源诱导的小鼠淋巴瘤和大鼠乳腺肿瘤的激活ras癌基因中发现。这些加合物被DNA修复蛋白o6 -烷基鸟嘌呤-DNA烷基转移酶去除。在胸腺中表达该蛋白的人类同源基因的转基因小鼠在暴露于n -甲基-n -亚硝基脲后可保护其不发生胸腺淋巴瘤。因此，单个人类DNA修复基因的转基因表达足以阻止化学致癌作用。体内DNA修复基因的转导可能揭示致癌机制，并提供针对已知致癌物的治疗保护。
Nitrosoureas form O6-alkylguanine-DNA adducts that are converted to G to A transitions, the mutation found in the activated ras oncogenes of nitrosourea-induced mouse lymphomas and rat mammary tumors. These adducts are removed by the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Transgenic mice that express the human homolog of this protein in the thymus were found to be protected from developing thymic lymphomas after exposure to N-methyl-N-nitrosourea. Thus, transgenic expression of a single human DNA repair gene is sufficient to block chemical carcinogenesis. The transduction of DNA repair genes in vivo may unravel mechanisms of carcinogenesis and provide therapeutic protection from known carcinogens.