GENOTOXIC CHEMICAL CARCINOGENS TARGET INDUCIBLE GENES IN-VIVO
GENOTOXIC CHEMICAL CARCINOGENS TARGET INDUCIBLE GENES IN-VIVO
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DOI：
10.1111/j.1749-6632.1994.tb52846.x
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发表时间：
1994-01-01
期刊：
影响因子：
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通讯作者：
DOHERTY, KA
中科院分区：
文献类型：
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作者：
HAMILTON, JW;MCCAFFREY, J;DOHERTY, KA
我们的实验室感兴趣的是致癌物诱导的DNA损伤是否在基因组中非随机分布-也就是说，{open_quotes}靶向{close_quotes}体内特定基因或基因区域。作为一个间接的措施是否发生在基因水平上的靶向，我们已经研究了致癌物质是否差异改变个别基因的表达。我们比较了模型遗传毒性致癌物的影响，主要是诱导链断裂，简单的烷基化，大的病变，或DNA交联的几个组成和诱导基因的表达在一个简单的体内系统，鸡胚。在对应于由每种化合物诱导的最大DNA损伤和修复的时间段的24小时时间段内，检查每种试剂对基因表达的影响。这些研究中使用的剂量代表了在96小时内不引起明显毒性但诱导显著DNA损伤水平的最大剂量。我们的研究结果表明，诱导基因的化学致癌物质的目标。我们推测这种效应可能是DNA损伤的结果，特异性改变了诱导基因启动子内的DNA-蛋白质相互作用。
Our laboratory is interested in whether carcinogen-induced DNA damage is distributed nonrandomly in the genome - that is, {open_quotes}targeted{close_quotes} to specific genes or gene regions in vivo. As an indirect measure of whether targeting occurs at the gene level, we have examined whether carcinogens differentially alter the expression of individual genes. We have compared the effects of model genotoxic carcinogens that principally induce either strand breaks, simple alkylations, bulky lesions, or DNA cross-links on the expression of several constitutive and inducible genes in a simple in vivo system, the chick embryo. Each agent was examined for its effects on gene expression over a 24 hour period corresponding to the period of maximal DNA damage and repair induced by each compound. The doses used in these studies represented the maximum doses that caused no overt toxicity over a 96 hour period but that induced significant levels of DNA damage. Our results demonstrate that inducible genes are targeted by chemical carcinogens. We hypothesize that such effects may be a result of DNA damage specifically altering DNA-protein interactions within the promoters of inducible genes.