Carmen Franken1, Nathalie Lambrechts2, Eva Govarts2, Gudrun Koppen2, Elly Den Hond3, Daniëlla Ooms2, Stefan Voorspoels2, Liesbeth Bruckers4, Ilse Loots5, Vera Nelen3, Isabelle Sioen6, Tim S Nawrot7, Willy Baeyens8, Nicolas Van Larebeke9, Greet Schoeters10. 1. Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. Electronic address: frankencarmen@gmail.com. 2. Flemish Institute for Technological Research (VITO), Mol, Belgium. 3. Provincial Institute for Hygiene, Antwerp, Belgium. 4. Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium. 5. Political and Social Sciences, University of Antwerp, Antwerp, Belgium. 6. Department of Public Health, Ghent University, Ghent, Belgium; Department of Food Safety and Food Quality, Ghent University, Ghent, Belgium. 7. Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; Department of Public Health & Primary Care, Leuven University, Leuven, Belgium. 8. Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. 9. Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium; Department of Radiotherapy and Nuclear Medicine, Ghent University, Ghent, Belgium. 10. Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND: In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown. AIM: The aim of this study was to identify if oxidative stress, assessed by excision of 8-hydroxydeoxyguanosine (8-OHdG) from damaged DNA, is an intermediate marker for the association between phthalate exposure and doctor-diagnosed asthma. MATERIAL AND METHODS: In 418 14-15-year-old youngsters, recruited as a representative sample of residents of Flanders (Belgium), personal exposure to phthalates was assessed by measuring phthalate metabolites in urine: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP) and mono-ethyl phthalate (MEP). Analysis of 8-OHdG in urine was used as a sensitive biomarker of oxidative stress at the level of DNA. The presence of doctor-diagnosed asthma was elicited by a self-administered questionnaire. Associations were assessed using multiple linear and logistic regression models. Mediation was tested using Baron and Kenny's regression approach. RESULTS: A significant increased risk of a youngster being diagnosed with asthma was found for both urinary MnBP (metabolite of dibutyl phthalate (DBP)) and the sum of the three di(2-ethylhexyl) phthalate metabolites (ΣDEHP=MEHP+MEHHP+MEOHP), with respective odds ratio of 1.84 [95% CI: 1.02, 3.32] for MnBP and 1.94 [95% CI: 1.07, 3.51] for ΣDEHP. In addition, we observed significant associations between all urinary phthalate metabolites and increased urinary levels of 8-OHdG. The associations were stronger in girls than in boys. We did not found evidence that 8-OHdG was associated with doctor-diagnosed asthma. CONCLUSION: The results of our study are in line with other findings from epidemiological surveys and raise further concern about DEHP and DBP as risk factors for asthma, however, the underlying mechanisms are not yet well understood.
BACKGROUND: In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown. AIM: The aim of this study was to identify if oxidative stress, assessed by excision of 8-hydroxydeoxyguanosine (8-OHdG) from damaged DNA, is an intermediate marker for the association between phthalate exposure and doctor-diagnosed asthma. MATERIAL AND METHODS: In 418 14-15-year-old youngsters, recruited as a representative sample of residents of Flanders (Belgium), personal exposure to phthalates was assessed by measuring phthalate metabolites in urine: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP) and mono-ethyl phthalate (MEP). Analysis of 8-OHdG in urine was used as a sensitive biomarker of oxidative stress at the level of DNA. The presence of doctor-diagnosed asthma was elicited by a self-administered questionnaire. Associations were assessed using multiple linear and logistic regression models. Mediation was tested using Baron and Kenny's regression approach. RESULTS: A significant increased risk of a youngster being diagnosed with asthma was found for both urinary MnBP (metabolite of dibutyl phthalate (DBP)) and the sum of the three di(2-ethylhexyl) phthalate metabolites (ΣDEHP=MEHP+MEHHP+MEOHP), with respective odds ratio of 1.84 [95% CI: 1.02, 3.32] for MnBP and 1.94 [95% CI: 1.07, 3.51] for ΣDEHP. In addition, we observed significant associations between all urinary phthalate metabolites and increased urinary levels of 8-OHdG. The associations were stronger in girls than in boys. We did not found evidence that 8-OHdG was associated with doctor-diagnosed asthma. CONCLUSION: The results of our study are in line with other findings from epidemiological surveys and raise further concern about DEHP and DBP as risk factors for asthma, however, the underlying mechanisms are not yet well understood.
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