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与职业性接触苯乙烯相关的 DNA 损伤、DNA 修复率以及细胞周期基因(TP53、p21(CDKN1A)、BCL2 和 BAX)的 mRNA 表达水平。

DNA damage, DNA repair rates and mRNA expression levels of cell cycle genes (TP53, p21(CDKN1A), BCL2 and BAX) with respect to occupational exposure to styrene.

机构信息

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Prague, Czech Republic.

出版信息

Carcinogenesis. 2011 Jan;32(1):74-9. doi: 10.1093/carcin/bgq213. Epub 2010 Oct 21.

Abstract

We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes. The workers were divided into low (<50 mg/m³) and high (>50 mg/m³) styrene exposure groups. We found negative correlations between mRNA expression of TP53, BCL2, BAX and styrene exposure (P < 0.001 for all parameters). In contrast, p21(CDKN1A) mRNA expression significantly increased with increasing styrene exposure (P = 0.001). SSBs and endonuclease III-sensitive sites increased with increasing mRNA levels of TP53 (P < 0.001 for both) and BCL2 (P = 0.038, P = 0.002, respectively), whereas the same parameters decreased with increasing mRNA levels of p21(CDKN1A) (P < 0.001, P = 0.007, respectively). γ-Irradiation-specific DNA repair rates increased with p21(CDKN1A) mRNA levels up to the low exposure level (P = 0.044). Our study suggests a possible relationship between styrene exposure, DNA damage and transcript levels of key cell cycle genes.

摘要

我们研究了一组 71 名苯乙烯暴露工人和 51 名对照个体的 DNA 损伤、DNA 修复率和细胞周期基因 TP53、p21(CDKN1A)、BCL2 和 BAX 的信使 RNA(mRNA)表达水平之间的关系。通过测量工作场所和血液中的苯乙烯浓度来评估暴露情况。在周围血淋巴细胞中分析了 DNA 损伤参数[测量为单链断裂(SSB)和内切酶 III 敏感位点]、γ-辐射特异性 DNA 修复率和研究基因的 mRNA 水平。工人被分为低(<50mg/m³)和高(>50mg/m³)苯乙烯暴露组。我们发现 TP53、BCL2、BAX 的 mRNA 表达与苯乙烯暴露呈负相关(所有参数 P<0.001)。相比之下,p21(CDKN1A)mRNA 表达随着苯乙烯暴露的增加而显著增加(P=0.001)。SSB 和内切酶 III 敏感位点随着 TP53(P<0.001)和 BCL2(P=0.038,P=0.002)mRNA 水平的增加而增加,而相同的参数随着 p21(CDKN1A)mRNA 水平的增加而降低(P<0.001,P=0.007)。γ-辐射特异性 DNA 修复率随着 p21(CDKN1A)mRNA 水平的增加而增加,直到低暴露水平(P=0.044)。我们的研究表明,苯乙烯暴露、DNA 损伤和关键细胞周期基因的转录水平之间可能存在关系。

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