Ryberg D, Hewer A, Phillips D H, Haugen A
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Cancer Res. 1994 Nov 15;54(22):5801-3.
The levels of aromatic/hydrophobic DNA adducts were analyzed in normal lung tissue from 63 lung cancer patients and examined in relation to exposure and genetic factors. Adduct levels were significantly higher in smokers than in nonsmokers, but among smokers the number of cigarettes smoked per day had only low significance for the variation in adduct levels. An inverse correlation was found between years of smoking and DNA adduct levels (r = 0.52, P = 0.001). Thus, patients with high adduct levels generally had shorter duration of smoking and/or lower smoking dose before the clinical onset of the disease, which fits expected behavior of cancer susceptible individuals. The data indicated an excess of individuals with glutathione S-transferase M1 deficiency among male patients with high adduct levels. Among females the DNA adduct levels were higher than in males when adjusted for smoking dose. There was a highly significant difference in the distribution of males and females when smokers were divided into quartile groups according to adducts per pack year (trend test: 2-sided P = 0.005). This may indicate that women are at greater risk of tobacco-induced lung cancer.
对63例肺癌患者的正常肺组织中芳香族/疏水性DNA加合物水平进行了分析,并研究了其与暴露因素和遗传因素的关系。吸烟者的加合物水平显著高于不吸烟者,但在吸烟者中,每天吸烟的支数对加合物水平的变化仅有较低的显著性影响。发现吸烟年限与DNA加合物水平呈负相关(r = 0.52,P = 0.001)。因此,加合物水平高的患者在疾病临床发病前通常吸烟时间较短和/或吸烟剂量较低,这符合癌症易感个体的预期行为。数据表明,加合物水平高的男性患者中谷胱甘肽S-转移酶M1缺乏的个体过多。在根据吸烟剂量进行调整后,女性的DNA加合物水平高于男性。当吸烟者根据每包年的加合物分为四分位数组时,男性和女性的分布存在高度显著差异(趋势检验:双侧P = 0.005)。这可能表明女性患烟草诱导肺癌的风险更大。