Induction of activation-induced cytidine deaminase by a not-directly mutagenic carcinogen: a novel potential molecular mechanism.
Induction of activation-induced cytidine deaminase by a not-directly mutagenic carcinogen: a novel potential molecular mechanism.
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非直接诱变致癌物诱导活化诱导的胞苷脱氨酶：一种新的潜在分子机制。
DOI：
10.1007/s12199-014-0382-x
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nakadate T.
中科院分区：
文献类型：
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作者：
Tatemichi M;Hata H;Nakadate T.
目的非直接致突变（艾姆斯致突变试验阴性）致癌物致癌活性的分子机制尚不完全清楚。鉴于最近发现体细胞中激活诱导的胞苷脱氨酶（AID）的异位表达在癌发生中起着关键作用，我们研究了几种已确定的非直接诱变致癌物是否诱导AID表达。方法我们制备了含有AID启动子的荧光素酶报告基因稳定表达的细胞。然后我们使用该系统检测了非遗传毒性致癌物：邻苯二甲酸丁苄酯、双酚A、邻苯二甲酸二(2-乙基己基)酯、氯化镉(Cd)和丁基羟基苯甲醚的AID启动子活性。结果结果显示Cd增加了AID启动子活性，并且实际上诱导了AID基因表达。结论镉是一种非直接致突变致癌物，具有诱导AID基因表达的潜力。 AID 基因，表明这可能代表镉致癌的一种新分子机制。
ObjectiveThe molecular mechanisms underlying the carcinogenic activity of not-directly mutagenic (Ames mutagenicity test-negative) carcinogens are not fully understood. Given recent findings that ectopic expression of activation-induced cytidine deaminase (AID) in somatic cells plays a critical role in carcinogenesis, we investigated whether several of the established not-directly mutagenic carcinogens induce AID expression.MethodsWe prepared cells with stable expression of luciferase reporter gene containing the promoter of AID. We then used this system to examine the AID promoter activity of the non-genotoxic carcinogen: butyl benzyl phthalate, bisphenol A, di (2-ethylhexyl) phthalate, cadmium chloride (Cd), and butylated hydroxyanisole.ResultsResults showed that Cd increased the promoter activity of AID and actually induced AID gene expression.ConclusionA not-directly mutagenic carcinogen, cadmium, has the potential to induce the AID gene, suggesting that this might represent a novel molecular mechanism of carcinogenesis of cadmium.