Section for Toxicology, Department of Chemical and Biological Working Environment, National Institute of Occupational Health, Oslo, Norway.
Lung Cancer. 2011 Mar;71(3):264-70. doi: 10.1016/j.lungcan.2010.09.006. Epub 2010 Oct 15.
Recent epidemiological studies have disputed whether females are at increased risk of lung cancer compared to males. However, several molecular studies are in support of an increased susceptibility to tobacco smoke carcinogens among females. Our earlier findings suggest that women display higher levels of smoking-induced bulky/hydrophobic DNA adducts which may be related to an increased expression of CYP1A1 in their lungs, compared to men. In this in vitro study, 11 lung adenocarcinoma cell lines, 6 of male and 5 of female origin, were exposed to benzo[a]pyrene, cigarette smoke condensate (CSC), or vehicle control. Subsequent expression analysis of genes in the polycyclic aromatic hydrocarbon bioactivation pathway was conducted with Real-Time RT-PCR. DNA adducts were measured in benzo[a]pyrene-exposed cells by ³²P-postlabelling analysis, and CYP1 activity was measured by EROD assay. Analysis of benzo[a]pyrene-DNA adducts showed higher levels of adducts in cell lines from women compared to cell lines from men (p=0.03). The results also revealed significant sex differences in CYP1A1 gene expression, both in untreated cells (p=0.03), and in cells exposed to benzo[a]pyrene (p=0.017) and cigarette smoke condensate (p=0.0043). In CSC-exposed cells, significantly higher levels of CYP1 activity was found in cell lines of female origin (p=0.049). These results are in support of the previously published in vivo data, providing evidence for a higher susceptibility to PAH of women's lungs.
最近的流行病学研究对女性与男性相比是否肺癌风险增加存在争议。然而，几项分子研究支持女性对烟草烟雾致癌物更易感性。我们之前的研究结果表明，与男性相比，女性显示出更高水平的吸烟诱导的大体积/疏水性 DNA 加合物，这可能与她们肺部中 CYP1A1 的表达增加有关。在这项体外研究中，用苯并[a]芘、香烟烟雾冷凝物（CSC）或载体对照处理 11 种肺腺癌细胞系，其中 6 种来源于男性，5 种来源于女性。然后用实时 RT-PCR 进行多环芳烃生物活化途径中基因的表达分析。通过 ³²P-后标记分析测量苯并[a]芘暴露细胞中的 DNA 加合物，并用 EROD 测定法测量 CYP1 活性。苯并[a]芘-DNA 加合物分析显示，女性细胞系中的加合物水平高于男性细胞系（p=0.03）。结果还显示，CYP1A1 基因表达在未处理细胞（p=0.03）和苯并[a]芘（p=0.017）和香烟烟雾冷凝物（p=0.0043）暴露的细胞中存在显著的性别差异。在 CSC 暴露的细胞中，女性来源的细胞系中 CYP1 活性水平显著升高（p=0.049）。这些结果支持之前发表的体内数据，为女性肺部对 PAH 的更高易感性提供了证据。
