Slyskova J, Dusinska M, Kuricova M, Soucek P, Vodickova L, Susova S, Naccarati A, Tulupova E, Vodicka P
Department of Experimental and Applied Genetics, Research Base of Slovak Medical University, Bratislava, Slovak Republic.
Mutat Res. 2007 Dec 1;634(1-2):101-11. doi: 10.1016/j.mrgentox.2007.06.012. Epub 2007 Aug 9.
Genotoxic effects related to exposure to styrene have been a matter of investigation for many years by employing markers of exposure, effect and susceptibility. The role of individual DNA-repair capacity in response to exposure to styrene may explain the controversial results so far obtained, but it is still scarcely explored. In the present study, we measured capacity to repair oxidative DNA damage in cell extracts obtained from 24 lamination workers occupationally exposed to styrene and 15 unexposed controls. The capacity to repair oxidative DNA damage was determined by use of a modified comet assay, as follows: HeLa cells, pre-treated with photosensitizer and irradiated with a halogen lamp in order to induce 7,8-dihydroxy-8-oxoguanine, were incubated with cell extracts from mononuclear leukocytes of each subject. The level of strand breaks reflects the removal of 7,8-dihydroxy-8-oxoguanine from substrate DNA by the enzymatic extract. In styrene-exposed subjects a moderate, non-significant increase in oxidative DNA repair was observed. Stratification for sex and smoking habit showed that unexposed males (P=0.010) and unexposed smokers (P=0.037) exhibited higher DNA-repair rates. The repair capacity did not correlate with parameters of styrene exposure and biomarkers of genotoxic effects (DNA strand breaks, N1-styrene-adenine DNA adducts, chromosomal aberrations and mutant frequencies at the HPRT locus). Significantly higher levels of DNA-repair capacity were observed in carriers of GSTM1-plus, compared to those with a deletion in GSTM1. The DNA-repair capacity was significantly lower in individuals with variant Gln/Gln genotype in XRCC1 Arg399Gln than in those with heterozygous Arg/Gln and wild-type Arg/Arg genotypes. Significantly lower repair capacity was also found in individuals with the wild-type Lys/Lys genotype in XPC Lys939Gln as compared with those homozygous for the Gln/Gln variant genotype.
多年来，通过使用接触、效应和易感性标志物，对与接触苯乙烯相关的遗传毒性效应进行了研究。个体DNA修复能力在接触苯乙烯反应中的作用可能解释了目前获得的有争议的结果，但仍鲜有研究。在本研究中，我们测量了从24名职业性接触苯乙烯的层压工人和15名未接触者的对照中获得的细胞提取物修复氧化性DNA损伤的能力。氧化性DNA损伤的修复能力通过使用改良彗星试验测定，具体如下：用光敏剂预处理HeLa细胞，并用卤素灯照射以诱导7,8-二羟基-8-氧代鸟嘌呤，然后将其与每个受试者单核白细胞的细胞提取物一起孵育。链断裂水平反映了酶提取物从底物DNA中去除7,8-二羟基-8-氧代鸟嘌呤的情况。在接触苯乙烯的受试者中，观察到氧化性DNA修复有适度但不显著的增加。按性别和吸烟习惯分层显示，未接触的男性（P = 0.010）和未接触的吸烟者（P = 0.037）表现出较高的DNA修复率。修复能力与苯乙烯接触参数和遗传毒性效应生物标志物（DNA链断裂、N1-苯乙烯-腺嘌呤DNA加合物、染色体畸变和HPRT位点的突变频率）无关。与GSTM1缺失的个体相比，GSTM1阳性携带者的DNA修复能力水平显著更高。与杂合子Arg/Gln和野生型Arg/Arg基因型个体相比，XRCC1 Arg399Gln中Gln/Gln基因型变体的个体DNA修复能力显著更低。与Gln/Gln变体基因型纯合子个体相比，XPC Lys939Gln中野生型Lys/Lys基因型个体的修复能力也显著更低。
