Statistical analysis of lacZ mutant frequency data from Muta™Mouse mutagenicity assays
Statistical analysis of lacZ mutant frequency data from Muta™Mouse mutagenicity assays
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DOI：
10.1093/mutage/13.3.249
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发表时间：
1998-05-01
期刊：
影响因子：
2.7
通讯作者：
Krewski, D
中科院分区：
文献类型：
--
作者：
Fung, KY;Douglas, GR;Krewski, D
转基因小鼠试验为研究啮齿动物不同组织的突变提供了前所未有的机会。在这篇文章中，使用肝脏和骨髓作为潜在的靶组织，系统地分析了基于大肠杆菌基因lacZ的穆塔（TM）小鼠致突变性试验的数据。评价了变异来源，包括平板（包装内反应）、包装反应（动物内）和动物的超二项式变异。尽管在平板水平几乎未检测到任何过度分散的证据，但在包装反应水平观察到有限的超二项式变异证据。然而，有更强有力的证据表明，在动物水平上过度分散。还在动物水平进行了突变频率随剂量增加而增加趋势的统计学检验。一个显着的增加趋势，暴露于N-亚硝基二苄胺后，在肝脏中检测到，但在骨髓中没有。使用逻辑模型进一步描述在N-亚硝基二苄胺处理的肝组织中观察到的剂量-反应关系。
Transgenic mouse assays have provided an unprecedented opportunity td study mutagenesis in diverse rodent tissues. In this article data from Muta(TM)Mouse mutagenicity assays based on the Escherichia coli gene lacZ were analyzed systematically using liver and bone marrow as potential target tissues. Sources of variation, including plates (within packaging reactions), packaging reactions (within animals) and animals, were evaluated for extra-binomial variation. Although hardly any evidence of overdispersion was detected at the plate level, limited evidence of extra-binomial variation was observed at the packaging reaction level. There was, however, much stronger evidence of overdispersion at the animal level. Statistical tests for increasing trend in mutant frequency with increasing dose were also performed at the animal level. A significant increasing trend following exposure to N-nitrosodibenzylamine was detected in liver but not in bone marrow. A logistical model was used to further describe the dose-response relationship observed in N-nitrosodibenzylamine-treated liver tissue.