Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacI transgenic rats and mice following exposure to aflatoxin B-1
Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacI transgenic rats and mice following exposure to aflatoxin B-1
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DOI：
10.1093/carcin/17.11.2347
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发表时间：
1996-11-01
期刊：
影响因子：
4.7
通讯作者：
Provost, GS
中科院分区：
文献类型：
--
作者：
Dycaico, MJ;Stuart, GR;Provost, GS
在λ/lacI（Big Blue（R））转基因C57 BL/6小鼠和F344大鼠中，研究了暴露于AF B（1）（黄曲霉毒素B-1）或DMSO载体后的体内突变。暴露14天后，取出肝脏进行DNA提取和随后的lad基因突变分析。小鼠腹腔注射2.5 mg/kg的AFB（1），与对照组相比，肝脏突变频率没有显著增加，从AFB收集的lad突变的DNA序列分析（1）-处理的小鼠显示出与先前观察到的自发小鼠肝突变谱相似的突变模式。相比之下，大鼠接受十分之一的小鼠AFB（1）剂量，其肝脏突变频率的诱导约为背景的20倍。对lad突变的测序也显示了溶媒组和AFB（1）组大鼠之间的光谱差异。在从AFB（1）处理的大鼠中分离的lad突变中观察到G：C->T：A颠换的大幅增加。这项工作是首次使用携带相同穿梭载体的转基因啮齿动物进行的多物种体内致突变性研究之一。这种多物种体内测定可能被证明在机理分析和风险评估领域是有价值的。
In vivo mutations were studied in lambda/lacI (Big Blue(R)) transgenic C57BL/6 mice and F344 rats following exposure to either AFB(1) (aflatoxin B-1) or DMSO vehicle. Fourteen days after exposure, livers were removed for DNA extraction and subsequent mutational analysis of the lad gene, Mice injected with a single i.p. dose of AFB(1) at 2.5 mg/kg did not show a significant increase in liver mutant frequency relative to vehicle-treated controls, DNA sequence analysis of lad mutations collected from the AFB(1)-treated mice showed a pattern of mutation similar to that of the previously observed spontaneous mouse liver mutational spectrum. In contrast, rats subjected to one-tenth the mouse AFB(1) dosage responded with an approximate 20-fold induction in liver mutant frequency over background, Sequencing of lad mutations also revealed spectral differences between vehicle- and AFB(1)-treated rats. A large increase in G:C-->T:A transversions was observed among lad mutations isolated from the AFB(1)-treated rats, This work is among the first multi-species in vivo mutagenicity studies using transgenic rodents harboring the same shuttle vector. Such multi-species in vivo assays may prove to be valuable in the areas of mechanistic analysis and risk assessment.