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Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture.

Pieters N, Koppen G, Smeets K, Napierska D, Plusquin M, De Prins S, Van De Weghe H, Nelen V, Cox B, Cuypers A, Hoet P, Schoeters G, Nawrot TS - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.

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.

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Association between mitochondrial DNA content and PAH exposure in winter and in summer.Four correlation plots are given, each indicating different PAH exposure, volatile PAHs in house dust in winter (A), non-volatile PAHs in house dust in winter (B), volatile PAHs in house dust in summer in (C) and non-volatile PAHs in house dust in summer in (D). Values of mitochondrial DNA content (mtDNAcn) are log transformed.
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pone-0063208-g002: Association between mitochondrial DNA content and PAH exposure in winter and in summer.Four correlation plots are given, each indicating different PAH exposure, volatile PAHs in house dust in winter (A), non-volatile PAHs in house dust in winter (B), volatile PAHs in house dust in summer in (C) and non-volatile PAHs in house dust in summer in (D). Values of mitochondrial DNA content (mtDNAcn) are log transformed.

Mentions: Blood mitochondrial DNA content was similar in men and women (0.96 vs 0.99, p = 0.48). We noticed significant season-by-PAH exposure interactions on mitochondrial DNA content. Therefore, we analyzed the data for summer and winter separately. In winter, both before (figure 2) and after (table 4) cumulative adjustment for gender, age, BMI and the consumption of grilled meat or fish, blood mitochondrial DNA content was inversely and independently correlated with the indoor PAH dust concentration. When the analysis was repeated separately for non-volatile and volatile PAHs, we found that the effect was mostly attributed to non-volatile PAHs (table 4). We found a decrease of 9.85% (95% CI: −15.16% to −4.2%, p = 0.002) in mitochondrial DNA content for each doubling in non-volatile PAH concentration and a 7.3% decrease (95% CI: −13.71% to −0.42%, p = 0.04) for a doubling in volatile PAH, when adjusted for aforementioned variables. In addition we ran a separate multivariate analysis using benzo(a)pyrene dust exposure. Each doubling in benzo(a)pyrene exposuse was associated with a 7.18% decrease (95%CI: −11.82% to −2.3%, p = 0.007) in mitochondrial DNA content. In summer, with adjustments applied as before, blood mitochondrial DNA content was not associated with indoor PAH.


Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture.

Pieters N, Koppen G, Smeets K, Napierska D, Plusquin M, De Prins S, Van De Weghe H, Nelen V, Cox B, Cuypers A, Hoet P, Schoeters G, Nawrot TS - PLoS ONE (2013)

Association between mitochondrial DNA content and PAH exposure in winter and in summer.Four correlation plots are given, each indicating different PAH exposure, volatile PAHs in house dust in winter (A), non-volatile PAHs in house dust in winter (B), volatile PAHs in house dust in summer in (C) and non-volatile PAHs in house dust in summer in (D). Values of mitochondrial DNA content (mtDNAcn) are log transformed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643917&req=5

pone-0063208-g002: Association between mitochondrial DNA content and PAH exposure in winter and in summer.Four correlation plots are given, each indicating different PAH exposure, volatile PAHs in house dust in winter (A), non-volatile PAHs in house dust in winter (B), volatile PAHs in house dust in summer in (C) and non-volatile PAHs in house dust in summer in (D). Values of mitochondrial DNA content (mtDNAcn) are log transformed.
Mentions: Blood mitochondrial DNA content was similar in men and women (0.96 vs 0.99, p = 0.48). We noticed significant season-by-PAH exposure interactions on mitochondrial DNA content. Therefore, we analyzed the data for summer and winter separately. In winter, both before (figure 2) and after (table 4) cumulative adjustment for gender, age, BMI and the consumption of grilled meat or fish, blood mitochondrial DNA content was inversely and independently correlated with the indoor PAH dust concentration. When the analysis was repeated separately for non-volatile and volatile PAHs, we found that the effect was mostly attributed to non-volatile PAHs (table 4). We found a decrease of 9.85% (95% CI: −15.16% to −4.2%, p = 0.002) in mitochondrial DNA content for each doubling in non-volatile PAH concentration and a 7.3% decrease (95% CI: −13.71% to −0.42%, p = 0.04) for a doubling in volatile PAH, when adjusted for aforementioned variables. In addition we ran a separate multivariate analysis using benzo(a)pyrene dust exposure. Each doubling in benzo(a)pyrene exposuse was associated with a 7.18% decrease (95%CI: −11.82% to −2.3%, p = 0.007) in mitochondrial DNA content. In summer, with adjustments applied as before, blood mitochondrial DNA content was not associated with indoor PAH.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.

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.

Show MeSH
Related in: MedlinePlus