Effect of genetic modification of acute inflammatory responsiveness on tumorigenesis in the mouse
Effect of genetic modification of acute inflammatory responsiveness on tumorigenesis in the mouse
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DOI：
10.1093/carcin/19.2.337
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发表时间：
1998-02-01
期刊：
影响因子：
4.7
通讯作者：
Ibanez, OM
中科院分区：
文献类型：
--
作者：
Biozzi, G;Ribeiro, OG;Ibanez, OM
两个不同的数量性状的双向选择育种开始从相同的遗传异质性小鼠群体。所得到的线的特征在于最大或最小的急性炎症反应性（AIR）：AIRmax和AIRmin线，分别是，并通过电阻或敏感性化学皮肤肿瘤发生：Car-R和Car-S线，分别。空气对s.c.的响应注射聚丙烯酰胺微珠后，通过局部渗出液中的细胞含量测量，AIRmax小鼠中的细胞含量比AIRmin小鼠高10倍。AIRmax和AIRmin的实际遗传力分别为0.26和0.008，是由7-11个数量性状基因座的加性效应决定的。低反应性在F1中占绝对优势，F2中48%的分离变异是由遗传因素引起的。这些发现是第一次证明生殖系基因对AIR的先天调节。两阶段启动（DMBA）-促进（TPA）方案诱导的皮肤肿瘤发生的易感性在AIRmax小鼠中低于AIRmin小鼠，肿瘤诱导率相差6倍。强烈的空气被发现与电阻，低ALR与肿瘤发生的易感性，在F2分离选择极端空气表型。因此，至少一些AIR QTL含有控制肿瘤发生的基因。与AIRmax和AIRmin系相比，Car-R和Car-S系的肿瘤表型差异更大，表明与AIR无关的QTL有助于宿主对肿瘤发生的反应。极端的表型/基因型的四个选定的线和已知的遗传组成，其基础人口，提供了新的可能性，以区别控制两个重要性状的基因/机制：空气和化学致瘤反应。合作项目将被优先考虑。AIRmax和Car-R小鼠肿瘤耐药基因的描述可能有助于人类肿瘤的流行病学和治疗。
Two distinct bidirectional selective breedings for quantitative traits were initiated from identical genetically heterogeneous mouse populations. The resulting lines are characterized by maximal or minimal acute inflammatory responsiveness (AIR): AIRmax and AIRmin lines, respectively, and by resistance or susceptibility to chemical skin tumorigenesis: Car-R and Car-S lines, respectively. The AIR response to s.c. injection of polyacrylamide microbeads, measured by cell content in the local exudate, was 10 times higher in AIRmax than in AIRmin mice. The response to selection was asymmetrical: the realized heritability was 0.26 in AIRmax and 0.008 in AIRmin, and resulted from the additive effect of 7-11 quantitative trait loci (QTL). Low responsiveness was globally dominant in F1 and 48% of F2 segregant variance was found to be due to genetic factors. These findings are the first demonstration of innate regulation of AIR by germ line genes. Susceptibility to skin tumorigenesis induced by a two-stage initiation (DMBA)-promotion (TPA) protocol was lower in AIRmax mice than in AIRmin mice, a 6-fold difference in tumor induction rate. Intense AIR was found to be associated with resistance, and low ALR with susceptibility to tumorigenesis, in F2 segregants chosen for extreme AIR phenotypes. At least some of the AIR QTLs therefore contain genes controlling tumorigenesis. Tumor phenotypes differed more in Car-R and Car-S than in AIRmax and AIRmin lines, indicating that QTLs unrelated to AIR, contribute to the host response to tumorigenesis. The extreme phenotypes/genotypes of the four selected lines and the known genetic constitution of their foundation population, offer new possibilities to discriminate the genes/mechanisms controlling two important traits: AIR and response to chemical tumorigenesis. Collaborative projects will be favorably considered. The description of tumor resistance genes in AIRmax and Car-R mice may be helpful for epidemiology and therapy of human cancer.