职业暴露于工业环境中的工人中与 DNA 修复和铅毒性相关的基因表达失调。
Expression deregulation of genes related to DNA repair and lead toxicity in occupationally exposed industrial workers.
机构信息
Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
出版信息
Int Arch Occup Environ Health. 2023 Dec;96(10):1333-1347. doi: 10.1007/s00420-023-02012-4. Epub 2023 Oct 7.
OBJECTIVE
Globally millions of people working in various industries and are exposed to different toxins which may affect their genetic stability and DNA integrity. Present study was designed to estimate the expression variation of genes related to DNA repair (XRCC1, PARP1) and lead toxicity (ALAD) in exposed industrial workers.
METHODS
About 200 blood samples were collected from workers of brick kiln, welding, furniture and paint industry (50/industry) along with age and gender matched controls. mRNA expression of genes was measured using RT-PCR. Serum levels of total ROS, POD, TBAR activity was calculated. Blood lead levels were estimated by atomic absorption spectrometer.
RESULTS
Relative expression of XRCC1 and PARP1 gene was significantly (P < 0.001) upregulated, while ALAD gene expression was downregulated in exposed group compared to control. Expression of XRCC1 and PARP1 was increased (P < 0.001) in exposed workers with > 30 year age compared to control with > 30 year age. Same was observed when < 30 year age group of control and exposed was compared. Likewise, XRCC1 and PARP1 expression was increased (P < 0.001) in exposed workers with > 30 year age compared to workers with < 30 year age. Whereas, ALAD gene showed significant (P < 0.01) decrease in > 30 year age workers compared to control of same age and exposed with < 30 year of age. Relative expression of XRCC1 and PARP1 was increased (P < 0.001) in exposed smokers compared to exposed non-smokers and control smokers. Whereas, ALAD gene expression reduced (P < 0.001) significantly in both groups. Blood lead content was higher (P < 0.001) in exposed group compared to control. Strong correlation was observed between XRCC1, PARP1 and ALAD gene versus age, total exposure duration, exposure per day and lead deposition. ROS, TBARS and POD activity was higher (P < 0.01) in exposed group compared to control group.
CONCLUSION
Present study suggested deregulation of genes related to DNA repair and lead intoxication in exposed group compared to controls. Strong correlation was observed between selected genes and demographic parameters. Present results revealed altered activity of oxidative stress markers which would induce oxidative damage to DNA integrity and limit the function of repair enzymes.
目的
全球数以百万计的人在不同行业工作，接触到不同的毒素，这些毒素可能会影响他们的遗传稳定性和 DNA 完整性。本研究旨在评估暴露于工业环境中的工人的 DNA 修复（XRCC1、PARP1）和铅毒性（ALAD）相关基因的表达变化。
方法
从砖窑、焊接、家具和油漆行业的工人（每个行业 50 人）中采集了约 200 份血液样本，并与年龄和性别匹配的对照组进行了比较。采用 RT-PCR 测量基因的 mRNA 表达。计算总 ROS、POD、TBAR 活性。采用原子吸收光谱仪估计血铅水平。
结果
与对照组相比，暴露组的 XRCC1 和 PARP1 基因表达显著上调（P<0.001），而 ALAD 基因表达下调。与对照组年龄>30 岁的人群相比，暴露组年龄>30 岁的人群中 XRCC1 和 PARP1 的表达增加（P<0.001）。当比较对照组和暴露组年龄<30 岁的人群时，也观察到了同样的情况。同样，与年龄<30 岁的暴露组相比，暴露组年龄>30 岁的人群中 XRCC1 和 PARP1 的表达增加（P<0.001）。然而，ALAD 基因在年龄>30 岁的工人中显著降低（P<0.01），与同一年龄的对照组和年龄<30 岁的暴露组相比。与暴露组非吸烟者相比，暴露组吸烟者的 XRCC1 和 PARP1 表达显著增加（P<0.001），而对照组吸烟者的 ALAD 基因表达显著降低（P<0.001）。与对照组相比，暴露组的血铅含量更高（P<0.001）。XRCC1、PARP1 和 ALAD 基因与年龄、总暴露时间、每天暴露时间和铅沉积之间存在强烈相关性。与对照组相比，暴露组的 ROS、TBARS 和 POD 活性更高（P<0.01）。
结论
与对照组相比，暴露组的 DNA 修复和铅中毒相关基因表达失调。选定基因与人口统计学参数之间存在很强的相关性。本研究结果表明，氧化应激标志物的活性改变会导致 DNA 完整性的氧化损伤，并限制修复酶的功能。
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