Increased Mitochondrial DNA Copy Number in Occupations Associated with Low-Dose Benzene Exposure

Carugno, Michele; Pesatori, Angela Cecilia; Dioni, Laura; Hoxha, Mirjam; Bollati, Valentina; Albetti, Benedetta; Byun, Hyang‐Min; Bonzini, Matteo; Fustinoni, Silvia; Cocco, Pierluigi; Satta, Giannina; Zucca, Mariagrazia; Merlo, Domenico Franco; Cipolla, Massimo; Bertazzi, Pier Alberto; Baccarelli, Andrea

doi:10.1289/ehp.1103979

Cited by 98 publications

(52 citation statements)

References 44 publications

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“…However, these studies have reported somewhat inconsistent results, possibly owing to variations in exposure concentration, exposure duration, type of exposure, and the dynamic balance between oxidative damage and anti-oxidative defense pathways. 20,21,34,35 For instance, exposure to low-level benzene and short-term exposure to traffic pollution were associated with increased mtDNA abundance, probably due to an adaptive biogenesis response to compensate moderate oxidative damage. 21,34 On the other hand, in an occupational setting where participants were exposed to high levels of elemental carbon and PM 10 (particulate matter with aerodynamic diameter ≤10 μm), Pavanello et al reported decreased levels of mtDNA abundance.…”

Section: Discussionmentioning

confidence: 99%

“…20,21,34,35 For instance, exposure to low-level benzene and short-term exposure to traffic pollution were associated with increased mtDNA abundance, probably due to an adaptive biogenesis response to compensate moderate oxidative damage. 21,34 On the other hand, in an occupational setting where participants were exposed to high levels of elemental carbon and PM 10 (particulate matter with aerodynamic diameter ≤10 μm), Pavanello et al reported decreased levels of mtDNA abundance. 35 Nevertheless, these studies focused on short-term exposures, which may not capture aggregated risk due to prolonged environmental exposure.…”

Section: Discussionmentioning

confidence: 99%

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Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance

et al. 2017

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Background Fine particulate matter (PM2.5) represents a mixture of components with potentially different toxicities. However, little is known about the relative effects of PM2.5 mass and PM2.5 components on mitochondrial DNA (mtDNA) abundance, which may lie on the pathway of PM2.5-associated disease. Methods We studied 646 elderly male participants in the Normative Aging Study from Greater Boston to investigate associations of long-term exposure to PM2.5 mass and PM2.5 components with mtDNA abundance. We estimated concentrations of pollutants for the 365-day preceding examination at each participant's address using spatial-and-temporal-resolved chemical transport models. We measured blood mtDNA abundance using RT-PCR. We applied a shrinkage-and-selection method (adaptive-LASSO) to identify components most predictive of mtDNA abundance, and fit multi-pollutant linear mixed-effects models with subject-specific intercept to estimate the relative effects of individual PM component. Results MtDNA abundance was negatively associated with PM2.5 mass in the previous year and—after adjusting for PM2.5 mass—several PM2.5 components, including organic carbon, sulfate (marginally) and nitrate. In multi-pollutant models including as independent variables PM2.5 mass and PM2.5 components selected by LASSO, nitrate was associated with mtDNA abundance. A standard deviation (SD) increase in annual PM2.5-associated nitrate was associated with a 0.12 SD (95% CI: -0.18; -0.07) decrease in mtDNA abundance. Analyses restricted to PM2.5 annual concentration below the current 1-year EPA standard produced similar results. Conclusions Long-term exposures to PM2.5-associated nitrate were related to decreased mtDNA abundance independent of PM2.5 mass. Mass alone may not fully capture the potential of PM2.5 to oxidize the mitochondrial genome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance

et al. 2017

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“…Normal mitochondrial function generates reactive oxygen species, and because of its proximal location, mtDNA is particularly vulnerable to oxidative damage. Effects of air pollution on mtDNA damage, including copy number variation,7 8‐hydroxy‐2′‐deoxyguanosine formation,8 and heteroplasmy,9 have been reported in human and animal studies. Recently, DNA methylation machinery was found in mitochondria,10 and mtDNA methylation levels have been shown to be associated with mitochondrial gene expression,11 which suggests possible roles for mtDNA methylation in controlling mitochondrial functions and biogenesis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability

Byun

Colicino

Trevisi

et al. 2016

JAHA

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BackgroundThe mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal‐rich particulates (particulate matter <2.5 µm in diameter [PM 2.5]) from welding in a boilermaker union and blood mtDNA methylation in relation to heart rate variability.Methods and ResultsForty‐eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM 2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D‐loop) and genes essential for ATP synthesis (MT‐TF and MT‐RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding‐work day, and mtDNA methylation experimental batch effect. The participants’ PM 2.5 exposure was significantly higher after a welding‐work day (mean 0.38 mg/m3) than the background personal level (mean 0.15 mg/m3, P<0.001). Blood mtDNA methylation in the D‐loop promoter was associated with PM 2.5 levels (β=−0.99%, SE=0.41, P=0.02). MT‐TF and MT‐RNR1 methylation was not associated with PM 2.5 exposure (β=0.10%, SE=0.45, P=0.82). Interaction of PM 2.5 exposure levels and D‐loop promoter methylation was significantly associated with markers of heart rate variability.ConclusionsBlood mtDNA methylation levels were negatively associated with PM 2.5 exposure and modified the adverse relationships between PM 2.5 exposure and heart rate variability outcomes.

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“…2 Thus, the mutation rate of mtDNA has been reported to be up to 15-fold higher than for nuclear DNA in response to DNA-damaging agents 3 such as UV, cigarette smoke, benzene, and ionizing radiation. [4][5][6] It has been hypothesized that mitochondria function and mtDNA damage are involved in carcinogenesis. 7 Studies have suggested that mitochondria possibly increase the number of mtDNA copies to compensate for mtDNA damage and mitochondrial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort

Hosnijeh

Lan

Rothman

et al. 2014

Blood

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Key Points• This study strengthens the previous observation of elevated mitochondrial DNA copy number and future risk of chronic lymphocytic leukemia.It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype-specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed significant increased risks of CLL (n 5 102) with increasing mtDNA copy number (odds ratio 5 1.34, 1.44, and 1.80 for quartiles 2-4, respectively; P trend 5 .001). mtDNA copy number was not associated with follow-up time, suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis. (Blood. 2014;124(4):530-535)

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Increased Mitochondrial DNA Copy Number in Occupations Associated with Low-Dose Benzene Exposure

Cited by 98 publications

References 44 publications

Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance

Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance

Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability

Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort

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