title: Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants that are formed in combustion processes. At the cellular level, exposure to PAHs causes oxidative stress and/or some of it congeners bind to DNA, which may interact with mitochondrial function. However, the influence of these pollutants on mitochondrial DNA (mtDNA) content remains largely unknown. We determined whether indoor exposure to PAHs is associated with mitochondrial damage as represented by blood mtDNA content. Blood mtDNA content (ratio mitochondrial/nuclear DNA copy number) was determined by real-time qPCR in 46 persons, both in winter and summer. Indoor PAH exposure was estimated by measuring PAHs in sedimented house dust, including 6 volatile PAHs and 8 non-volatile PAHs. Biomarkers of oxidative stress at the level of DNA and lipid peroxidation were measured. In addition to the epidemiologic enquiry, we exposed human TK6 cells during 24 h at various concentrations (range: 0 to 500 µM) of benzo(a)pyrene and determined mtDNA content. Mean blood mtDNA content averaged (± SD) 0.95 ± 0.185. The median PAH content amounted 554.1 ng/g dust (25(th)-75(th) percentile: 390.7-767.3) and 1385 ng/g dust (25(th)-75(th) percentile: 1000-1980) in winter for volatile and non-volatile PAHs respectively. Independent for gender, age, BMI and the consumption of grilled meat or fish, blood mtDNA content decreased by 9.85% (95% CI: -15.16 to -4.2; p = 0.002) for each doubling of non-volatile PAH content in the house dust in winter. The corresponding estimate for volatile PAHs was -7.3% (95% CI: -13.71 to -0.42; p = 0.04). Measurements of oxidative stress were not correlated with PAH exposure. During summer months no association was found between mtDNA content and PAH concentration. The ability of benzo(a)pyrene (range 0 µM to 500 µM) to lower mtDNA content was confirmed in vitro in human TK6 cells. Based on these findings, mtDNA content can be a target of PAH toxicity in humans.
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Nicky
authors: N
authors: Pieters
authors: Gudrun
authors: G
authors: Koppen
authors: Karen
authors: K
authors: Smeets
authors: Dorota
authors: D
authors: Napierska
authors: Michelle
authors: M
authors: Plusquin
authors: Sofie
authors: S
authors: De Prins
authors: Hendrik
authors: H
authors: Van De Weghe
authors: Vera
authors: V
authors: Nelen
authors: Bianca
authors: B
authors: Cox
authors: Ann
authors: A
authors: Cuypers
authors: Peter
authors: P
authors: Hoet
authors: Greet
authors: G
authors: Schoeters
authors: Tim S
authors: TS
authors: Nawrot
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000032:analysis / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000097:blood*; D004032:Diet; D004391:Dust / Q000032:analysis*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry*; D018384:Oxidative Stress; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000494:pharmacology*; D012621:Seasons
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D004272:DNA, Mitochondrial; D004391:Dust; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene
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