Genotoxic and Apoptotic effects of Heavy Metal Mixture on Human Aortic Vascular Smooth Muscle Cell Line

Öz

Objective: Heavy metals are the most common pollutants with specific gravity greater than 5 g cm^-3. Human exposure to heavy metals occurs mostly through the consumption of food and water containing heavy metals. Metals that enter the body via drinking water may cause genotoxicity and various diseases. Therefore, permissible limits of heavy metals in water for human consumption have been determined by laws and regulations. Our study aimed to investigate the effects of a mix of metals (Cu, Zn, Pb and Fe) at permissible limits in drinking water on aortic smooth muscle cells (TG-HA-VSMC) with at molecular level.

Material-Method: A metal mix at the permissible concentration for drinking water and 10-fold higher concentration were exposed to human aortic smooth muscle for 24 and 48 hours, and gene expression of antioxidant enzymes, heat-shock proteins and apoptosis pathway were investigated in addition to RAPD-DNA polymorphism.

Results: It was determined that heavy metal exposure caused increase in the DNA polymorphism, apoptotic cell ratios and enhanced antioxidant and apoptosis pathway gene expression in cells.

Conclusion: In conclusion, the mix consisting of heavy metals at permissible limits in drinking water has been shown to cause oxidative stress, genotoxicity and apoptosis in human aortic smooth muscle cells. Considering that apoptosis in vascular smooth muscle cells plays a role in the pathophysiology of diseases such as arteriosclerosis and hypertension, we believe it would be beneficial to assess these limits through extensive investigations in further studies.

Anahtar Kelimeler

• Human aortic vascular smooth muscle cell,cardiovascular toxicity,heavy metal,gen expression

Genotoxic and Apoptotic Effects of Heavy Metal Mixture on Human Aortic Vascular Smooth Muscle Cell Line

Öz

Amaç: Ağır metaller özgül ağırlıkları 5g cm^-3’ten yüksek olan en yaygın kirleticilerdir. Insanların ağır metallere maruziyeti genellikle ağır metal içeren su ve besinlerin tüketilmesi yolu ile olmaktadır. Içme suyu yolu ile vücuda giren metaller genotoksisite ve çeşitli hastalıklara neden olurlar. Bu nedenle insani tüketim amaçlı kullanılan sularda ağır metallerin kabul edilebilir limitleri kanun ve yönetmelikler ile belirlenmiştir. Bizim çalışmamız içme suyunda izin verilen limitlerde metal miksinin (Cu, Zn, Pb ve Fe) insan aort düz kas hücrelerinde (TG-HA-VSMC) etkilerini moleküler düzeyde araştırmayı amaçlamıştır.

Materyal-Metot: İnsan aort düz kas hücrelerine içme sularında izin verilen düzey ve 10 kat yüksek konsantrasyonda metal miksi 24 ve 48 saat süre ile uygulandı ve RAPD-DNA polimorfizmine ilaveten antioksidan enzimler, ısı şok proteinleri ve apoptoz yolak genlerinin ifadeleri belirlendi.

Bulgular: Ağır metal uygulamasının DNA polimorfizminde, apoptotic hücre oranında, antioksidan ve apoptoz yolağı gen ifadelerinde artışa neden olduğu belirlendi. 

Anahtar Kelimeler

• İnsan aort vasküler düz kas hücresi,ağır metal,kardiyovasküler toksisite,gen ifadesi

Kaynakça

1. 1. Khan S, Cao Q, Zheng YM, Huang YZ, Zhu, YG. Health risks of heavy metals in contaminated soils and food crops irrigated with wastewater in Beijing, China. Environmental pollution. 2008; 152(3): 686-92.
2. 2. Påhlsson AMB. Toxicity of heavy metals (Zn, Cu, Cd, Pb) to vascular plants. Water, air and soil pollution. 1989; 47(3-4): 287-319.
3. 3. Wuana RA, Okieimen FE. Heavy metals in contaminated soils: a review of sources, chemistry, risks and best available strategies for remediation. Isrn Ecology. 2011; 402647.
4. 4. Järup L. Hazards of heavy metal contamination. British medical bulletin. 2003; 68(1): 167-182.
5. 5. Panigrahi, A. Heavy metal toxicity. Everyman’s Science (Indian Science Congress). 2014; 68(6): 418.
6. 6. Britton RS, Leicester KL, Bacon BR. Iron toxicity and chelation therapy. International journal of hematology. 2002; 76(3): 219-28.
7. 7. Doganlar O, Doganlar ZB. Effects of a mixture of volatile organic compounds on total DNA and gene expression of heat shock proteins in Drosophila melanogaster. Archives of environmental contamination and toxicology. 2015; 68(2): 395-404.
8. 8. Doğanlar ZB, Doğanlar O, Tabakçıoğlu K. Genotoxic effects of heavy metal mixture in Drosophila melanogaster: expressions of heat shock proteins, RAPD profiles and mitochondrial DNA sequence. Water, air and soil pollution. 2014; 225(9): 2104.

9. 9. von Harsdorf R, Li PF, Dietz R. Signaling pathways in reactive oxygen species–induced cardiomyocyte apoptosis. Circulation. 1999; 99(22): 2934-41.
10. 10. Dimmeler S, Zeiher AM. Reactive oxygen species and vascular cell apoptosis in response to angiotensin II and pro-atherosclerotic factors. Regulatory peptides. 2000; 90(1-3); 19-25.
11. 11. Boyle JJ. Vascular smooth muscle cell apoptosis in atherosclerosis. International journal of experimental pathology. 1999; 80(4): 197-203.
12. 12. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nature medicine. 2006;. 12(9): 1075.