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

使用源自 Dark-Agouti 和 Wistar/Furth 祖细胞的速度同源品系的大鼠绘制对化学诱导舌癌的敏感和/或抗性基因图谱

• 批准号: 11470399
• 负责人: KITANO Motoo
• 金额: $ 9.54万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470399/
• 关键词: Dark-Agouti rats; Wistar; Furth rats; Tongue carcinoma (TC); Chemical carcinogenesis; Susceptible genes to TC; Resistant genes to TC; Congenic rats; Alleles; ポジショナルクローニング; 4NQO誘発癌

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.

我们最近报告说，4-硝基醇1-氧化物（4NQO）诱导的大鼠对舌癌（TC）的敏感性大大变化，这取决于生物体的遗传背景。在本研究中，为了绘制编码4NQO催化酶的NQO1，我们研究了大鼠中NQO1的DNA序列分析，用于检测NQO1的多态性。结果，我们发现了DA和WF菌株之间NQO1的遗传差异。这种遗传差异表征了单核苷酸多态性（SNP），该核苷酸多态性（SNP）在核苷酸位置的Da大鼠和WF大鼠中的T中显示了c 121，该核苷酸的t在NQO1结构基因的5'-Fanking区域中存在。此外，通过使用此SNP的PCR-RFLP分析，我们还发现，在ChR 19上的D19RAT15和D19RAT90之间的NQO1位于大约17厘米处。此外，我们还揭示了NQO1内含子3的DNA序列在DA和WF中的NQO1的内含子3的长度比NQO的280-BP更长。我们的研究可能使能够确定特定疾病的候选基因，并在阐明大鼠模型实验的机制以及人类疾病中发挥重要作用，通过指代小鼠和人类染色体的同步区域。

项目成果

Kitano M,Tanuma J,Hirayama Y,LiT-J,Hirano M,Tomita I,Semba I..: "Green tea and rat tongue carcinogenesis(2): mutation of p53 gene during 4NQO-induced carcinogenesis in the Dark-Agouti rat"Reports of Kagoshima University Project: Interactive Studies on Foo

Kitano M、Tanuma J、Hirayama Y、LiT-J、Hirano M、Tomita I、Semba I..：“绿茶与大鼠舌癌发生（2）：4NQO 诱导暗刺豚鼠致癌过程中 p53 基因的突变

Kanbara k, Tanuma J, Gotoh K, Kitano M, Nakashima H, et al.: "Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134"AIDS Res Human Restrovir. 17. 615-622 (2001)

Kanbara k、Tanuma J、Gotoh K、Kitano M、Nakashima H 等人：“对 CXCR4 拮抗剂 T134 具有抗性的人类免疫缺陷病毒株的生物学和遗传特征”AIDS Res Human Restrovir。

Motoo Kitano: "Host genes controlling the susceptibility and resistance to squamous cell carcinoma of the tongue in a rat model"Pathology Intern.. 50. 353-362 (2000)

Motoo Kitano：“宿主基因控制大鼠模型中舌鳞状细胞癌的易感性和抗性”病理学实习.. 50. 353-362 (2000)

Yoshikazu Hirayama, Toshikazu Ushijima, Takashi Kuramoto, Motoo Kitano, Takashi Sugimura and Minako Nagao: "Linkage mapping of the rat Msh2 DNA mismatch repair gene on chromosome 6"Exp. Anim.. 48. 63-34 (1999)

Yoshikazu Hirayama、Toshikazu Ushijima、Takashi Kuramoto、Motoo Kitano、Takashi Sugimura 和 Minako Nagao：“6 号染色体上大鼠 Msh2 DNA 错配修复基因的连锁图谱”Exp。

Gabriel Landini, Yoshikazu Hirayama, Tie-Jun Li and Motoo Kitano: "Increased fractal complexity of the epithelial-connective tissue interface in the tongue of 4NQO-treated rats"Pathol. Res. Pract.. 196. 251-258 (2000)

Gabriel Landini、Yoshikazu Hirayama、Tie-Jun Li 和 Motoo Kitano：“4NQO 治疗大鼠舌头上皮结缔组织界面的分形复杂性增加”Pathol。