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.

我们最近报道，4-硝基喹啉1-氧化物（4 NQO）诱导的大鼠舌癌（TC）的易感性根据生物体的遗传背景而有很大差异。在本研究中，为了定位NQO 1编码的4 NQO催化酶，我们研究了大鼠NQO 1的DNA序列分析，以检测NQO 1的多态性。结果表明，DA株和WF株的NQO 1基因存在遗传差异。这种遗传差异的特征是单核苷酸多态性（SNP），其在NQO 1结构基因的5 '侧翼区的核苷酸位置121处显示DA大鼠中的C和WF大鼠中的T。此外，通过利用该SNPs的PCR-RFLP分析，我们还发现大鼠的NQO 1位于Chr 19上D19 Rat 15和D19 Rat 90之间的约17-cM处。此外，我们还发现，在NQO 1的内含子3的DNA序列在DA和WF株比一般已知的NQO 1长280-bp。我们的研究可能会使特定疾病的候选基因定位成为可能，并通过参照小鼠和人类染色体的同线区域，不仅对大鼠模型的实验机制，而且对人类疾病的机制发挥重要作用。

项目成果

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。

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)

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。

Kenji Kanbara, Setsuko Sato, Jun-ichi Tanuma, Hirokazu Tamamura, Kazuyo Gotoh, Manabu Yoshimori, Taisei Kana-moto, Motoo Kitano, Nobutaka Fujii and Hideki Nakashima: "Biological and genetic characterization of a human immunodeficiency virus strain resista

Kenji Kanbara、Setsuko Sato、Jun-ichi Tanuma、Hirokazu Tamamura、Kazuyo Gotoh、Manabu Yoshimori、Taisei Kana-moto、Motoo Kitano、Nobutaka Fujii 和 Hideki Nakashima：“人类免疫缺陷病毒抗性株的生物学和遗传特征