Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Prague, Czech Republic.
Carcinogenesis. 2011 Jan;32(1):74-9. doi: 10.1093/carcin/bgq213. Epub 2010 Oct 21.
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.
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。