Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes.
Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes.
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转基因小鼠中化学诱导的前胃乳头状瘤携带突变的人类 c-Ha-ras 转基因。
DOI：
10.11501/3089113
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发表时间：
1992
期刊：
影响因子：
11.2
通讯作者：
M. Katsuki
中科院分区：
文献类型：
--
作者：
K. Ando;A. Saitoh;O. Hino;R. Takahashi;M. Kimura;M. Katsuki
前胃乳头状瘤和皮肤乳头状瘤的诱导非常有效的化学致癌剂甲基亚硝基脲（MNU）在转基因小鼠（rasH 2系）携带的人杂交c-Ha-ras基因，编码原型p21基因产物的单剂量管理。前胃乳头状瘤的发生率是剂量依赖性的;当腹腔注射50 mg/kg MNU时，所有的转基因小鼠（56/56）在给药后12周内发生前胃乳头状瘤，而5和0.5mg/kg的MNU分别在19只小鼠中的2只和19只小鼠中的1只中诱发乳头状瘤。56只转基因小鼠中有9只（16%）在被咬伤或抓伤的部位也发生了皮肤乳头状瘤。在给予50 mg/kg MNU后，77只非转基因同窝仔中仅1只发生前胃乳头状瘤，在给予MNU后12周内未出现皮肤乳头状瘤。在56只受影响的转基因小鼠中的55只（98%）中发生的肿瘤中的转基因（整合拷贝数，5-6）含有至少1个拷贝的转基因，该转基因通过第12密码子的体细胞点突变（从GGC（Gly）到GAC（Asp））激活。由于迄今为止在转基因小鼠的正常组织中从未检测到转基因的第12或第61密码子处的体细胞点突变，因此转基因的这些突变激活是肿瘤特异性事件。还检测了这些活化的转基因的RNA表达。从这些结果中，它表明，体细胞突变激活的人c-Ha-ras转基因在这些转基因小鼠的MNU管理诱导的前胃和皮肤乳头状瘤的发生中起着致病作用。这种转基因小鼠为诱导或抑制乳头状瘤形成的化学物质提供了独特的筛选系统。
Forestomach papillomas and skin papillomas were induced very efficiently by a single dose administration of the chemical carcinogen methylnitrosourea (MNU) in transgenic mice (rasH2 line) carrying human hybrid c-Ha-ras genes, which encode the prototype p21 gene product. The incidence of forestomach papillomas was dose dependent; when 50 mg/kg of MNU were administered i.p., all of the transgenic mice (56 of 56) developed forestomach papillomas within 12 weeks after administration, whereas 5 and 0.5 mg/kg of MNU induced papillomas in 2 of 19 and 1 of 19 mice, respectively. Nine of 56 transgenic mice (16%) also developed skin papillomas at sites wounded by bites or scratches. Only 1 of 77 nontransgenic littermates developed forestomach papillomas after administration of 50 mg/kg of MNU, and no skin papillomas appeared within 12 weeks after MNU administration. The transgenes (integrated copy number, 5-6) in the tumors developed in 55 of 56 affected transgenic mice (98%) contained at least 1 copy of the transgene that was activated by somatic point mutation at the 12th codon, from GGC (Gly) to GAC (Asp). Because somatic point mutations at the 12th or 61st codon of transgenes have never been detected in normal tissues of transgenic mice thus far examined, these mutational activations of transgenes are tumor-specific events. RNA expression of these activated transgenes was also detected. From these results, it is suggested that somatic mutational activation of the human c-Ha-ras transgene plays a causative role in the occurrence of forestomach and skin papillomas induced by MNU administration in these transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress papillomagenesis.
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DOI：
10.1016/0165-1110(87)90021-2
发表时间：
1987
期刊：
Mutation research
影响因子：
--
作者：
Guerrero,I;Pellicer,A
通讯作者：
Pellicer,A
影响因子：
56.9
作者：
RAPPOLEE, DA;MARK, D;WERB, Z
通讯作者：
WERB, Z
O6-甲基鸟嘌呤突变和修复是不均匀的。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Topal,MD;Eadie,JS;Conrad,M
通讯作者：
Conrad,M
肿瘤前小鼠乳腺组织中 H-ras 癌基因的激活。
影响因子：
8
作者：
Kumar,R;Medina,D;Sukumar,S
通讯作者：
Sukumar,S