Rossnerova Andrea, Elzeinova Fatima, Chvojkova Irena, Honkova Katerina, Sima Michal, Milcova Alena, Pastorkova Anna, Schmuczerova Jana, Rossner Pavel, Topinka Jan, Sram Radim J
Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic; Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
Environ Pollut. 2023 Apr 15;323:121290. doi: 10.1016/j.envpol.2023.121290. Epub 2023 Feb 17.
Air pollution is a dominant environmental exposure factor with significant health consequences. Unexpectedly, research in a heavily polluted region of the Czech Republic, with traditional heavy industry, revealed repeatedly the lowest frequency of micronuclei in the season with the highest concentrations of air pollutants including carcinogenic benzo[a]pyrene (B[a]P). Molecular findings have been collected for more than 10 years from various locations of the Czech Republic, with differing quality of ambient air. Preliminary conclusions have suggested adaptation of the population from the polluted locality (Ostrava, Moravian-Silesian Region (MSR)) to chronic air pollution exposure. In this study we utilize the previous findings and, for the first time, investigate micronuclei (MN) frequency by type: (i) centromere positive (CEN+) MN, representing chromosomal losses, and (ii) centromere negative (CEN-) MN representing chromosomal breaks. As previous results indicated differences between populations in the expression of XRCC5, a gene involved in the non-homologous end-joining (NHEJ) repair pathway, possible variations in epigenetic settings in this gene were also investigated. This new research was conducted in two seasons in the groups from two localities with different air quality levels (Ostrava (OS) and Prague (PG)). The obtained new results show significantly lower frequencies of chromosomal breaks in the OS subjects, related to the highest air pollution levels (p < 0.001). In contrast, chromosomal losses were comparable between both groups. In addition, significantly lower DNA methylation was found in 14.3% of the analyzed CpG loci of XRCC5 in the population from OS. In conclusion, the epigenetic adaptation (hypomethylation) in XRCC5 involved in the NHEJ repair pathway in the population from the polluted region, was suggested as a reason for the reduced level of chromosomal breaks. Further research is needed to explore the additional mechanisms, including genetic adaptation.
空气污染是一个主要的环境暴露因素，会对健康造成重大影响。出人意料的是，在捷克共和国一个有传统重工业的重度污染地区进行的研究反复表明，在空气污染物（包括致癌性苯并[a]芘（B[a]P））浓度最高的季节，微核的出现频率最低。在过去10多年里，从捷克共和国不同地点收集了分子研究结果，这些地点的环境空气质量各不相同。初步结论表明，来自污染地区（俄斯特拉发，摩拉维亚-西里西亚地区（MSR））的人群对慢性空气污染暴露产生了适应性。在本研究中，我们利用先前的研究结果，首次按类型调查微核（MN）频率：（i）着丝粒阳性（CEN+）微核，代表染色体丢失；（ii）着丝粒阴性（CEN-）微核，代表染色体断裂。由于先前的结果表明，参与非同源末端连接（NHEJ）修复途径的基因XRCC5在不同人群中的表达存在差异，因此还研究了该基因表观遗传状态的可能变化。这项新研究在两个空气质量水平不同的地区（俄斯特拉发（OS）和布拉格（PG））的两组人群中进行了两个季节的调查。获得的新结果显示，与最高空气污染水平相关的OS组受试者的染色体断裂频率显著更低（p < 0.001）。相比之下，两组之间的染色体丢失情况相当。此外，在OS人群中，所分析的XRCC5的14.3%的CpG位点的DNA甲基化水平显著更低。总之，污染地区人群中参与NHEJ修复途径的XRCC5的表观遗传适应性（低甲基化）被认为是染色体断裂水平降低的原因。需要进一步研究以探索包括基因适应性在内的其他机制。
