Musak Ludovit, Soucek Pavel, Vodickova Ludmila, Naccarati Alessio, Halasova Erika, Polakova Veronika, Slyskova Jana, Susova Simona, Buchancova Janka, Smerhovsky Zdenek, Sedikova Jana, Klimentova Gabriela, Osina Oto, Hemminki Kari, Vodicka Pavel
Department of Medical Biology, Comenius University Bratislava, Jessenius Faculty of Medicine, Malá hora 4, 03754 Martin, Slovak Republic.
Mutat Res. 2008 May 10;641(1-2):36-42. doi: 10.1016/j.mrfmmm.2008.02.007. Epub 2008 Mar 4.
We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.5+/-1.8% vs. 1.7+/-1.2%, respectively). The differences between groups (ANOVA) were borderline significant (F=2.6, P=0.055). Chromosomal aberrations were higher in subjects with GSTT1-null (2.4+/-1.7%) than in those with GSTT1-plus genotype (1.8+/-1.4%; F=7.2, P=0.008). Considering individual groups, this association was significant in smoking exposed workers (F=4.4, P=0.040). Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010). Both chromatid- and chromosome-type aberration frequencies were mainly affected by exposure and smoking status. Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1.25, P=0.081) polymorphisms. Chromosome-type aberrations were lowest in individuals bearing the EPHX1 genotype conferring the high activity (OR 0.38, 95%CI 0.15-0.98, P=0.045). Present results show that exposed individuals in the tire production, who smoke, exhibit higher chromosomal aberrations frequencies, and the extent of chromosomal damage may additionally be modified by relevant polymorphisms.
我们评估了一家轮胎厂177名接触外源性物质的工人以及172名对照者淋巴细胞中的染色体畸变情况，并将其与他们的遗传背景相关联。研究了编码生物转化酶的基因中的9种多态性以及参与主要DNA修复途径的基因中的9种多态性对染色体损伤的可能调节作用。染色体畸变频率在接触外源性物质的吸烟者中最高，在未接触外源性物质的非吸烟者中最低（分别为2.5±1.8%和1.7±1.2%）。组间差异（方差分析）接近显著（F = 2.6，P = 0.055）。GSTT1基因缺失的受试者的染色体畸变率（2.4±1.7%）高于GSTT1基因阳性基因型的受试者（1.8±1.4%；F = 7.2，P = 0.008）。就个体分组而言，这种关联在吸烟的接触外源性物质的工人中显著（F = 4.4，P = 0.040）。与具有中等活性（1.7±1.2%）和高活性基因型（1.5±1.2%）的个体相比，具有低活性EPHX1基因型的个体表现出显著更高的染色体畸变率（2.3±1.6%；F = 4.7，P = 0.010）。染色单体型和染色体型畸变频率主要受接触情况和吸烟状态影响。二元逻辑回归分析显示，染色单体型畸变频率受NBS1 Glu185Gln多态性调节（比值比4.26，95%置信区间1.38 - 13.14，P = 0.012），并且在一定程度上受XPD Lys751Gln多态性调节（比值比0.16，95%置信区间0.02 - 1.25，P = 0.081）。具有高活性EPHX1基因型的个体的染色体型畸变率最低（比值比0.38，95%置信区间0.15 - 0.98，P = 0.045）。目前的结果表明，轮胎生产中吸烟的接触外源性物质的个体表现出更高的染色体畸变频率，并且染色体损伤程度可能还会因相关多态性而改变。
