Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from B6C3F1 mice exposed to cumene.
Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from B6C3F1 mice exposed to cumene.
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DOI：
10.1177/0192623308320280
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发表时间：
2008-07
影响因子：
1.5
通讯作者：
Lahousse SA
中科院分区：
文献类型：
--
作者：
Hong HH;Ton TV;Kim Y;Wakamatsu N;Clayton NP;Chan PC;Sills RC;Lahousse SA
枯烯处理的B6 C3 F1小鼠肺泡/细支气管腺瘤和癌的发生率显著高于对照组。我们评估了这些肺肿瘤中K-ras和p53基因的点突变，这些基因在人类中经常发生突变。K-ras和p53突变通过PCR扩增的DNA从石蜡包埋的肿瘤中分离的循环测序检测。K-ras基因突变在枯烯诱发的肺癌中检出率为87%，主要突变为第1外显子第12位密码子G → T转换和第2外显子第61位密码子A → G转换。56%枯烯诱发的肿瘤中P53蛋白表达，52%肿瘤中P53基因突变。主要突变是外显子5，密码子155 G到A的转换和密码子133 C到T的转换。在自发性肿瘤中未检测到p53突变，7例K-ras突变中1例（14%）。枯烯诱导的肺癌显示4号染色体p16基因附近（13%）和6号染色体K-ras基因附近（12%）的杂合性丢失（洛）。在自发性肺癌和正常肺组织中均未发现洛缺失。在肺肿瘤中鉴定的突变模式表明，DNA损伤和基因组不稳定性可能是暴露于枯烯的小鼠中突变谱和肺癌发展的促成因素。
The incidences of alveolar/bronchiolar adenomas and carcinomas in cumene-treated B6C3F1 mice were significantly greater than those of the controls. We evaluated these lung neoplasms for point mutations in the K-ras and p53 genes that are often mutated in humans. K-ras and p53 mutations were detected by cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded neoplasms. K-ras mutations were detected in 87 % cumene-induced lung neoplasms, and the predominant mutations were exon 1 codon 12 G to T transversions and exon 2 codon 61 A to G transitions. P53 protein expression was detected by immunohistochemistry in 56 % cumene-induced neoplasms and mutations were detected in 52 % neoplasms. The predominant mutations were exon 5, codon 155 G to A transitions and codon 133 C to T transitions. No p53 mutation and one of 7 (14 %) K-ras mutation was detected in spontaneous neoplasms. Cumene-induced lung carcinomas showed loss of heterozygosity (LOH) on chromosome 4 near the p16 gene (13 %) and on chromosome 6 near the K-ras gene (12 %). No LOH was observed in spontaneous carcinomas or normal lung tissues examined. The pattern of mutations identified in the lung tumors suggests that DNA damage and genomic instability may be contributing factors to the mutation profile and development of lung cancer in mice exposed to cumene.
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影响因子：
11.2
作者：
Le Calvez, F;Mukeria, A;Hainaut, P
通讯作者：
Hainaut, P
影响因子：
10.4
作者：
Gut, I;Nedelcheva, V;Tichavska, B
通讯作者：
Tichavska, B
影响因子：
4.7
作者：
Patel, AC;Anna, CH;Devereux, TR
通讯作者：
Devereux, TR
影响因子：
3.8
作者：
Hong, HL;Ton, TV;Sills, RC
通讯作者：
Sills, RC
影响因子：
2.8
作者：
Hong, Hue-Hua L.;Dunnick, June;Sills, Robert C.
通讯作者：
Sills, Robert C.