Congying Zheng, Sergey Shaposhnikov, Andrew Collins, Gunnar Brunborg, Amaya Azqueta, Sabine A S Langie, Maria Dusinka, Jana Slyskova, Pavel Vodicka, Frederik-Jan van Schooten, Stefano Bonassi, Mirta Milic, Irene Orlow, Roger Godschalk
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引用次数: 0
摘要
核苷酸切除修复(NER)对于修复外源性和内源性基因毒素造成的DNA大块病变和交联至关重要。将 DNA 修复作为生物标志物的研究数量有限,因此,欧洲 COST 行动 hCOMET(CA15132)的主要目标之一就是收集和分析具有 NER 活性数据的研究资料库。该数据库由 738 个个体组成,这些个体来自 5 个使用基于彗星的体外 DNA 修复测定法进行群体研究的实验室。对外周血单核细胞(PBMC)中的 NER 活性数据进行了归一化处理,并将其与各种宿主相关因素(包括性别、年龄、体重指数(BMI)和吸烟习惯)相关联。这种多方面的分析发现,女性参与者的核酸还原酶活性明显高于男性(1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002)。年龄较大(大于 30 岁)的受试者 NER 活性较高,年龄的影响在最年长的女性,尤其是 70 岁以上的女性中最为明显(P = 0.001)。体重指数正常(< 25 kg/m2)的女性的核辐射强度最高,而超重男性(体重指数≥ 25 kg/m2)的核辐射强度最低。没有发现吸烟的独立影响。按性别和体重指数分层后,吸烟男性的净核反应堆更高(P = 0.017)。较高或较低的修复能力对生物学的影响尚不清楚;将 DNA 修复作为一种生物标志物纳入分子流行病学试验应能阐明健康与疾病状况之间的联系。
A pooled analysis of host factors that affect nucleotide excision repair in humans.
Nucleotide excision repair (NER) is crucial for repairing bulky lesions and crosslinks in DNA caused by exogenous and endogenous genotoxins. The number of studies that have considered DNA repair as a biomarker is limited, and therefore one of the primary objectives of the European COST Action hCOMET (CA15132) was to assemble and analyze a pooled database of studies with data on NER activity. The database comprised 738 individuals, gathered from 5 laboratories that ran population studies using the comet-based in vitro DNA repair assay. NER activity data in peripheral blood mononuclear cells (PBMCs) were normalized and correlated with various host-related factors, including sex, age, body mass index (BMI), and smoking habits. This multifaceted analysis uncovered significantly higher NER activity in female participants compared to males (1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002). Higher NER activity was seen in older subjects (> 30 years), and the effect of age was most pronounced in the oldest females, particularly those over 70 years (P = 0.001). Females with a normal BMI (< 25 kg/m2) exhibited the highest levels of NER, whereas the lowest NER was observed in overweight males (BMI ≥ 25 kg/m2). No independent effect of smoking was found. After stratification by sex and BMI, higher NER was observed in smoking males (P = 0.017). The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status.
期刊介绍:
Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.