Protection by dietary compounds against mutation in a transgenic rodent
Protection by dietary compounds against mutation in a transgenic rodent
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DOI：
10.1093/jn/131.11.3082s
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发表时间：
2001-11-01
影响因子：
4.2
通讯作者：
de Boer, JG
中科院分区：
文献类型：
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作者：
de Boer, JG
遗传毒性和潜在致癌作用最相关的生物标志物之一是突变的发生。数据表明，致癌物在诱导肿瘤和突变方面对靶组织具有高度特异性。这种特异性可能反映了对组织特异性代谢活化、器官特异性环境或两者的依赖性。因此，理想情况下，突变应该在真实的动物中而不是在细胞培养系统中测定。lacl转基因啮齿动物模型提供了这样的系统。我们已经使用这个模型来调查组织，物种和性别特异性的突变诱导选定的膳食致癌物，并检查如何一些化合物可能会改变突变的诱导。我们已经研究了使用几种化学物质的突变，包括饮食杂环胺2-氨基-1-甲基-6-苯基咪唑[4，5-B]吡啶（PhIP），环境重要的芳烃苯并[a]芘和食品污染物黄曲霉毒素B-1。我们已经证明，这些化学品的致突变效力可以通过其他饮食化合物调节，包括绿色茶和共轭亚油酸，以及二恶英2，3，7，8-四氯二苯并[B，e][1，4]二恶英（TCDD）。这些结果表明，转lacl基因啮齿动物是一个有用的模型，在体内研究化学预防。
One of the most relevant biomarkers of genotoxicity and, potentially, carcinogenesis is the occurrence of mutations. Data indicate that carcinogens are highly specific with regard to their target tissue in inducing both tumors and mutations. This specificity may reflect the dependence on tissue-specific metabolic activation, the organ-specific environment or both. Ideally, therefore, mutation should be determined in a real animal rather than in a cell culture system. The lacl transgenic rodent model provides such a system. We have used this model to investigate tissue, species and sex specificity of mutation induced by selected dietary carcinogens and to examine how some compounds may alter the induction of mutation. We have studied mutation using several chemicals, including the dietary heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the environmentally important aromatic hydrocarbon benzo[a]pyrene and the food contaminant aflatoxin B-1. We have shown that the mutagenic potency of these chemicals can be modulated by other dietary compounds, including green tea and conjugated linoleic acid, and the dioxin 2,3,7,8-tetrachlorodibenzo[b,e][1,4]dioxin (TCDD). These results demonstrate that the lacl transgenic rodent is a useful model for the study of chemoprevention in vivo.