Angel J M, Beltrán L, Minda K, Rupp T, DiGiovanni J
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville 78957, USA.
Mol Carcinog. 1997 Oct;20(2):162-7. doi: 10.1002/(sici)1098-2744(199710)20:2<162::aid-mc2>3.0.co;2-p.
It has been known for many years that there are dramatic differences in the susceptibility of mouse stocks and strains to two-stage skin carcinogenesis and that these differences are due the animals' responsiveness to tumor-promoting agents. In earlier studies using several inbred mouse strains, we found that susceptibility to skin tumor promotion by phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) is a multigenic trait. To extend this work, we conducted a genome scan of (C57BL/6 x DBA/2)F1 x C57BL/6 mice previously scored for sensitivity to skin tumor promotion by TPA. As a result of this scan, we now report an association of increased TPA promotion susceptibility with inheritance of the DBA/2 alleles of markers on the distal portion of mouse chromosome 9. Additional linkage analyses using (C57BL/6 x DBA/2)F2 and B x D recombinant inbred mice confirmed this association and suggested that a TPA promotion susceptibility locus maps near D9Mit51 (LODw = 4.1). We designated this locus promotion susceptibility locus 1 (Ps/1).
多年来人们已经知道，不同品系和种类的小鼠对两阶段皮肤致癌作用的易感性存在显著差异，并且这些差异归因于动物对肿瘤促进剂的反应性。在早期使用几种近交系小鼠品系的研究中，我们发现对佛波酯如12-O-十四酰佛波醇-13-乙酸酯（TPA）的皮肤肿瘤促进作用的易感性是一种多基因性状。为了扩展这项工作，我们对先前已对TPA诱导皮肤肿瘤促进作用的敏感性进行评分的（C57BL/6×DBA/2）F1×C57BL/6小鼠进行了基因组扫描。作为这次扫描的结果，我们现在报告TPA促进作用易感性增加与小鼠9号染色体远端标记的DBA/2等位基因的遗传相关。使用（C57BL/6×DBA/2）F2和B×D重组近交小鼠进行的额外连锁分析证实了这种相关性，并表明一个TPA促进作用易感性基因座定位在D9Mit51附近（LODw = 4.1）。我们将这个基因座命名为促进作用易感性基因座1（Ps/1）。
