Genetic alterations in brain tumors following 1,3-butadiene exposure in B6C3F1 mice.
Genetic alterations in brain tumors following 1,3-butadiene exposure in B6C3F1 mice.
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B6C3F1 小鼠暴露于 1,3-丁二烯后脑肿瘤的遗传改变。
DOI：
10.1080/01926230590922848
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发表时间：
2005
影响因子：
1.5
通讯作者：
Sills,RobertC
中科院分区：
文献类型：
--
作者：
Kim,Yongbaek;Hong,Hue-HuaL;Lachat,Yan;Clayton,NatashaP;Devereux,TheodoraR;Melnick,RonaldL;Hegi,MonikaE;Sills,RobertC
在美国国家毒理学计划（NTP）生物测定中，B6C3F1小鼠的神经系统很少成为化学致癌的目标。然而，在暴露于625 ppm 1,3-丁二烯的B6C3F1小鼠中观察到6个恶性胶质瘤和2个神经母细胞瘤（NTP技术报告288和434）。这些小鼠脑肿瘤被评估关于在人类脑肿瘤中观察到的遗传改变的概况。p53肿瘤抑制基因的改变是常见的。3/6的恶性胶质瘤和2/2的神经母细胞瘤存在错义突变，并伴有杂合性缺失。大多数突变发生在p53基因外显子5-8，为G→A过渡，不涉及CpG位点。在5/5的恶性胶质瘤和1/1的神经母细胞瘤中观察到ink4a /Arfgene位点的杂合性缺失，而pten（磷酸酶和紧张素同源物）基因位点不受缺失的影响。2例神经母细胞瘤中有1例h -ras密码子61突变，而在恶性胶质瘤中未观察到h -ras突变。在500多个国家毒理学规划研究中，仅有1例对照小鼠出现脑瘤。该恶性胶质瘤未显示p53基因k -和h -突变改变的证据。观察到的特定遗传改变很可能是由1,3-丁二烯治疗诱导或选择的，从而导致小鼠脑肿瘤的发展。观察到的发现部分类似于在人类脑肿瘤中报道的基因改变。
The nervous system of the B6C3F1 mouse has rarely been a target for chemical carcinogenesis in the National Toxicology Program (NTP) bioassays. However, 6 malignant gliomas and 2 neuroblastomas were observed in B6C3F1 mice exposed to 625 ppm 1,3-butadiene (NTP technical reports 288 and 434). These mouse brain tumors were evaluated with regard to the profile of genetic alterations that are observed in human brain tumors. Alterations in thep53tumor suppressor gene were common. Missense mutations were observed in 3/6 malignant gliomas and 2/2 neuroblastomas and were associated with loss of heterozygosity. Most of the mutations occurred in exons 5–8 of thep53gene and were G → A transitions, and did not involve CpG sites. Loss of heterozygosity at theInk4a/Arfgene locus was observed in 5/5 malignant gliomas and 1/1 neuroblastoma, while thePTEN(phosphatase and tensin homologue) gene locus was unaffected by deletions. One of 2 neuroblastomas had a mutation in codon 61 ofH-ras, whileH-rasmutations were not observed in the malignant gliomas examined. Only 1 brain tumor has been reported from control mice of over 500 NTP studies. This malignant glioma showed no evidence of alterations in thep53gene orK- andH-rasmutations. It is likely that the specific genetic alterations observed were induced or selected for by 1,3-butadiene treatment that contributed to the development of mouse brain tumors. The observed findings are similar in part to the genetic alterations reported in human brain tumors.