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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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Mean mitochondrial DNA content in response to benzo(a)pyrene.Mean mitochondrial DNA (mtDNA) content of human TK6 cells exposed to 0; 0.05; 0.5; 5; 50 and 500 µM benzo(a)pyrene (BAP). Data are presented as mean ± SD; n = 3. *p<0.05 vs control (0 µM BAP); **p<0.01 vs. control (Analysis of variance: Kruskall-Wallis). Jonckheere-Terpstra test showed a significant (p = 0.0011) decrease over the exposure range.
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pone-0063208-g003: Mean mitochondrial DNA content in response to benzo(a)pyrene.Mean mitochondrial DNA (mtDNA) content of human TK6 cells exposed to 0; 0.05; 0.5; 5; 50 and 500 µM benzo(a)pyrene (BAP). Data are presented as mean ± SD; n = 3. *p<0.05 vs control (0 µM BAP); **p<0.01 vs. control (Analysis of variance: Kruskall-Wallis). Jonckheere-Terpstra test showed a significant (p = 0.0011) decrease over the exposure range.

Mentions: Human TK6 cells, exposed for 24 h to different concentrations of benzo(a)pyrene (0 to 500 µM benzo(a)pyrene) showed a significant dose-dependent decrease in mitochondrial DNA content. The concentration of 0.5 µM and higher showed significant decreases in comparison with the control group and the cells exposed to the lowest concentration of 0.05 µM benzo(a)pyrene (figure 3). The Jonckheere-Terpstra test showed a significant decrease over the different exposures (p = 0.0011). In S9 treated cells no decrease in mitochondrial DNA content was observed over the exposure range. TK6 cells viability and number of dead and living cells are given in table 6. Cell viability was comparable for all conditions, however, since the total number of living cells decreased with higher benzo(a)pyrene exposure, exposure to benzo(a)pyrene does not cause acute cytotoxicity but suppresses cell growth.


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)

Mean mitochondrial DNA content in response to benzo(a)pyrene.Mean mitochondrial DNA (mtDNA) content of human TK6 cells exposed to 0; 0.05; 0.5; 5; 50 and 500 µM benzo(a)pyrene (BAP). Data are presented as mean ± SD; n = 3. *p<0.05 vs control (0 µM BAP); **p<0.01 vs. control (Analysis of variance: Kruskall-Wallis). Jonckheere-Terpstra test showed a significant (p = 0.0011) decrease over the exposure range.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3643917&req=5

pone-0063208-g003: Mean mitochondrial DNA content in response to benzo(a)pyrene.Mean mitochondrial DNA (mtDNA) content of human TK6 cells exposed to 0; 0.05; 0.5; 5; 50 and 500 µM benzo(a)pyrene (BAP). Data are presented as mean ± SD; n = 3. *p<0.05 vs control (0 µM BAP); **p<0.01 vs. control (Analysis of variance: Kruskall-Wallis). Jonckheere-Terpstra test showed a significant (p = 0.0011) decrease over the exposure range.
Mentions: Human TK6 cells, exposed for 24 h to different concentrations of benzo(a)pyrene (0 to 500 µM benzo(a)pyrene) showed a significant dose-dependent decrease in mitochondrial DNA content. The concentration of 0.5 µM and higher showed significant decreases in comparison with the control group and the cells exposed to the lowest concentration of 0.05 µM benzo(a)pyrene (figure 3). The Jonckheere-Terpstra test showed a significant decrease over the different exposures (p = 0.0011). In S9 treated cells no decrease in mitochondrial DNA content was observed over the exposure range. TK6 cells viability and number of dead and living cells are given in table 6. Cell viability was comparable for all conditions, however, since the total number of living cells decreased with higher benzo(a)pyrene exposure, exposure to benzo(a)pyrene does not cause acute cytotoxicity but suppresses cell growth.

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