Kure E H, Ryberg D, Hewer A, Phillips D H, Skaug V, Baera R, Haugen A
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Carcinogenesis. 1996 Oct;17(10):2201-5. doi: 10.1093/carcin/17.10.2201.
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 32P-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.
人类肺癌在p53基因的G:C碱基对处表现出较高频率的颠换突变，这可能是香烟烟雾成分（最显著的是苯并[a]芘）导致DNA损伤的结果。我们研究了p53突变谱和疏水性DNA加合物水平的性别差异。从115例非小细胞肺癌肿瘤中获取肿瘤组织，使用聚合酶链反应（PCR）和单链构象多态性分析检测p53基因（外显子4至9）的突变改变。我们之前已检测过肺癌中的外显子5至8。外显子4和9的序列分析显示，近20%的突变位于外显子4和9。通过32P后标记分析法分析了55例患者非肿瘤性肺组织中疏水性DNA加合物的水平。尽管女性接触香烟烟雾致癌物的水平低于男性，但女性患者中G:C→T:A突变的频率更高，平均疏水性DNA加合物水平也更高。移码突变在女性中比在男性中更常见（分别为30%和15%）。这些初步发现支持了流行病学证据，即女性患烟草诱导肺癌的风险可能比男性更高。
