Title

 

Authors

C. Pellacani¹, A. Buschini ², S. Galati ², F. Mussi ², S. Franzoni ², L. G. Costa ^1,3.
 
¹Dep. of Human Anatomy, Pharmacology, and Forensic Sciences, University of Parma
MedicalSchool, Parma, Italy
²Dep. of Genetics, Biology of Microorganisms, Anthropology, Evolution, University of
Parma, Parma, Italy
³Dep. of Environmental and Occupational Health Sciences, University of Washington,
Seattle, Washington, USA 

 

Abstract

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants whose levels in the environment and in human tissues have increased in the past decades. These compounds have been used in many commercial products as polyurethane foam, textiles and variety of other plastic materials, for their ability to slow ignition and rate of fire.  Several studies have shown that exposure to PBDEs may cause developmental neurotoxicity, endocrine dysfunction and reproductive disorders. In spite of their widespread distribution and potential adverse health effects, only few studies have addressed the potential genotoxicity of PBDEs. In the present study we evaluated the genotoxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and decabrominated diphenyl ether (BDE-209) in human SK-N-MC neuroblastoma cells. Genotoxicity was studied using the alkaline version of the Comet assay. The results show that BDE-47 and BDE-209 (5-20 μM) are able to induce genotoxic effects in human SK-N-MC cells at two different exposure time (4 and 24h). Both PBDEs caused a concentration-dependent increase in DNA damage at 4 h, and BDE-47 appears to be more potent than BDE-209. When measured of 24h, DNA damage induced by two compounds was significantly decreased, suggesting a potential repair of damaged DNA. To determine the role of oxidative stress in DNA damage, SK-N-MC cells were pre-treated with melatonin (100 μM, 4h) prior to treatment with PBDEs (20 μM). The antioxidant melatonin significantly decreased DNA damage caused by BDE-47 and BDE-209, suggesting that these compounds damage DNA by inducing oxidative stress. Specific oxidatively generated damage to DNA was also measured by using a modified version of the Comet assay with the repair enzyme formamidopyrimidine glycosylase (FPG); this enzyme recognizes a particular kind of oxidative damage along the nucleotide chain where it creates a break. The results show that BDE-47 and BDE-209 induce base oxidation, revealed by FPG. Altogether these data suggest that BDE-47 and BDE-209 may cause oxidative damage to DNA at micromolar concentrations.