P53 mutations in lung tumours: Relationship to gender and lung DNA adduct levels
P53 mutations in lung tumours: Relationship to gender and lung DNA adduct levels
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DOI：
10.1093/carcin/17.10.2201
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发表时间：
1996-10-01
期刊：
影响因子：
4.7
通讯作者：
Haugen, A
中科院分区：
文献类型：
--
作者：
Kure, EH;Ryberg, D;Haugen, A
人肺癌表现出高频率的颠换突变的G：C碱基对的p53基因，可能是由香烟烟雾成分，最显着的苯并[a]芘的DNA损伤的结果。我们研究了p53突变谱和疏水DNA加合物水平的性别差异。从115例非小细胞肺癌肿瘤中获得肿瘤组织，并使用PCR和单链构象多态性分析检查p53基因（外显子4-9）的突变改变。我们以前检查了肺癌的外显子5-8。外显子4和9的序列分析显示，几乎20%的突变位于外显子4和9。用P-32后标记法检测了55例非肿瘤肺组织中DNA加合物的含量。女性患者G：C-->T：A突变频率和平均疏水DNA加合物水平均高于男性患者，尽管女性吸烟致癌物暴露水平低于男性患者，但移码突变在女性患者中比男性患者更常见（30%对15%）。这些初步研究结果支持了流行病学证据，即妇女可能比男子更容易患上烟草引起的肺癌。
Human lung cancer exhibits a high frequency of transversion mutations at G:C base pairs of the p53 gene, possibly the result of DNA damage by cigarette smoke constituents, most notably benzo[a]pyrene. We have investigated gender differences in the p53 mutational spectrum and levels of hydrophobic DNA adducts. Tumour tissue was obtained from 115 non-small cell lung cancer tumours and examined for mutational alterations in the p53 gene (exons 4-9) using PCR and single-strand conformational polymorphism analysis. We have previously examined exons 5-8 in lung cancer. Sequence analysis of exons 4 and 9 revealed that almost 20% of the mutations were located in exons 4 and 9. The levels of hydrophobic DNA adducts in non-tumorous lung tissue of 55 of the patients Were analyzed by the P-32-postlabelling assay. There were both a higher frequency of G:C-->T:A mutations and a higher average hydrophobic DNA adduct level in females than in male patients, even though the level of exposure to carcinogens from cigarette smoking was lower among the females than among the males, Frameshift mutations were more common in women than in men (30 versus 15%). These preliminary findings lend support to epidemiological evidence that women may be at greater risk than men of contracting tobacco-induced lung cancer.