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谷胱甘肽 S - 转移酶 M1(GSTM1)和谷胱甘肽 S - 转移酶 T1(GSTT1)基因拷贝数变异与职业性电离辐射暴露的核电站工人染色体畸变的关联

Association of GSTM1 and GSTT1 Copy Number Variation with Chromosomal Aberrations in Nuclear Power Plant Workers Exposed to Occupational Ionizing Radiation.

作者信息

Lee Joong Won, Lee Younghyun, Kim Yang Jee

机构信息

Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Republic of Korea.

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunghyang University, 22, Soonchunhyango-ro, Asan-si 31538, Republic of Korea.

出版信息

Toxics. 2025 Jan 22;13(2):73. doi: 10.3390/toxics13020073.

Abstract

Exposure to low-dose ionizing radiation in occupational settings raises concerns about chromosomal aberrations (CAs) and their potential impact on genomic stability. Copy number variations (CNVs), structural genomic changes, influence susceptibility to environmental stressors and radiation-induced damage. This study analyzed CAs in 180 nuclear power plant workers exposed to occupational radiation and 45 controls, stratified by GSTM1 and GSTT1 CNVs. Workers exhibited significantly higher frequencies of chromatid-type and chromosome-type aberrations, of 5.47 and 3.01 per 500 cells, respectively, compared to 3.57 and 0.64 in controls ( < 0.001 for both). In the relatively high-exposure group, chromatid-type aberrations decreased with increasing GSTM1 and GSTT1 copy numbers. For GSTM1, individuals with zero copies showed 6.37 ± 3.47 aberrations per 500 cells, compared to 5.02 ± 3.05 for one copy and 4.67 ± 2.40 for two or more copies ( = 0.06). A similar trend was observed for GSTT1, with 6.00 ± 3.29 aberrations per 500 cells for zero copies, 5.38 ± 2.79 for one copy, and 4.11 ± 4.26 for two or more copies ( = 0.05). Poisson regression analysis further supported these findings after adjusting for potential confounders such as age, smoking status, and alcohol intake. Workers with null genotypes exhibited a 1.36-fold increase in chromatid-type aberrations compared to those with higher copy numbers under relatively high-exposure conditions, suggesting a synergy effect between GSTM1 and GSTT1 null genotypes in modulating radiation-induced aberrations. These findings underscore the role of genetic susceptibility, particularly involving GSTM1 and GSTT1 CNVs, in modulating radiation-induced chromosomal damage. The observed gene-environment interaction in the relatively high-exposure group suggests that pre-existing CNVs contribute to chromosomal instability under radiation exposure.

摘要

职业环境中接触低剂量电离辐射引发了人们对染色体畸变(CA)及其对基因组稳定性潜在影响的担忧。拷贝数变异(CNV)作为基因组结构变化,会影响对环境应激源和辐射诱导损伤的易感性。本研究分析了180名接触职业辐射的核电站工人和45名对照者的染色体畸变情况,并按谷胱甘肽S-转移酶M1(GSTM1)和谷胱甘肽S-转移酶T1(GSTT1)拷贝数变异进行分层。与对照组每500个细胞中分别为3.57和0.64的染色单体型和染色体型畸变频率相比,工人的染色单体型和染色体型畸变频率显著更高,分别为每500个细胞5.47和3.01(两者均P<0.001)。在相对高暴露组中,染色单体型畸变随GSTM1和GSTT1拷贝数增加而减少。对于GSTM1,零拷贝个体每500个细胞显示6.37±3.47个畸变,而单拷贝个体为5.02±3.05个,两个或更多拷贝个体为4.67±2.40个(P = 0.06)。GSTT1也观察到类似趋势,零拷贝个体每500个细胞有6.00±3.29个畸变,单拷贝个体为5.38±2.79个,两个或更多拷贝个体为4.11±4.26个(P = 0.05)。在调整年龄、吸烟状况和酒精摄入量等潜在混杂因素后,泊松回归分析进一步支持了这些发现。在相对高暴露条件下,与拷贝数较高的个体相比,基因型缺失的工人染色单体型畸变增加了1.36倍,这表明GSTM1和GSTT1基因型缺失在调节辐射诱导的畸变方面存在协同效应。这些发现强调了遗传易感性的作用,特别是涉及GSTM1和GSTT1拷贝数变异,在调节辐射诱导的染色体损伤方面。在相对高暴露组中观察到的基因-环境相互作用表明,预先存在的拷贝数变异在辐射暴露下会导致染色体不稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1350/11860863/14d782b3ff97/toxics-13-00073-g001.jpg

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