Maps of susceptible and/or resistant genes to chemically induced tongue carcinomas using the rat derived from a speed congenic strain originating from the Dark-Agouti and Wistar/Furth progenitors

我们最近报道，大鼠对4-硝基喹啉-1-氧化物(4NQO)诱发的舌癌(TCS)的易感性因生物的遗传背景而有很大差异。在本研究中，为了定位编码4NQO催化酶的NQO1，我们对大鼠的NQO1进行了DNA序列分析，以检测NQO1的多态性。结果发现DA株和WF株的NQO1基因存在遗传差异。这种遗传差异表现为单核苷酸多态(SNPs)，DA大鼠为C，WF大鼠为T，位于NQO1结构基因5‘侧翼区的第121位核苷酸。此外，通过利用这些SNPs进行的PCR-RFLP分析，我们还发现大鼠的NQO1位于Chr 19上D19Rat15和D19Rat90之间约17 cM的位置。此外，我们还发现在DA和WF品系中，NQO1内含子3的DNA序列比通常所知的NQO1长280bp。我们的研究可能使精确定位特定疾病的候选基因成为可能，并通过参考小鼠和人类染色体的同线区域，在阐明大鼠模型实验机制以及人类疾病机制方面发挥重要作用。

We have recently reported that the susceptibility of rats to tongue cancers (TCs) induced by 4-nitroquinoline 1-oxide (4NQO) substantially varies depending on the genetic background of organisms. In present study, to map NQO1 encoding the catalytic enzyme of 4NQO, we have investigated DNA sequence analysis of NQO1 in rats for detecting polymorphisms of NQO1. As a result, we have found genetic difference of NQO1 between DA and WF strains. This genetic difference has characterized single nucleotide polymorphisms (SNPs) which shows a C in DA rat and a T in WF rat at nucleotide position 121, which exists in the 5'-flanking region of NQO1 structural gene. Furthermore, by PCR-RFLP analysis utilizing this SNPs, we also have found that NQO1 in rats locates on about 17-cM between D19Rat15 and D19Rat90 on Chr 19. In addition, we also have revealed that DNA sequence at intron 3 of NQO1 is 280-bp longer in DA and WF strains than that of NQO1 known generally. Our study may make it possible to pinpoint the candidate genes for particular diseases, and play an important role in throwing light on the mechanism not only of the experiments of the rat models, but also human diseases, by referring to the syntenic regions of the mouse and human chromosomes.