Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Aug 22:4:87.
doi: 10.3389/fcell.2016.00087. eCollection 2016.

Exposure to Inorganic Arsenic Is Associated with Increased Mitochondrial DNA Copy Number and Longer Telomere Length in Peripheral Blood

Syeda S Ameer  1 , YiYi Xu  1 , Karin Engström  2 , Huiqi Li  1 , Pia Tallving  1 , Barbro Nermell  3 , Analia Boemo  4 , Luis A Parada  5 , Lidia G Peñaloza  4 , Gabriela Concha  6 , Florencia Harari  3 , Marie Vahter  3 , Karin Broberg  3
Affiliations

Exposure to Inorganic Arsenic Is Associated with Increased Mitochondrial DNA Copy Number and Longer Telomere Length in Peripheral Blood

Syeda S Ameer et al. Front Cell Dev Biol. .

Abstract

Background: Exposure to inorganic arsenic (iAs) through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn) and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity.

Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N = 264, 89% females) and one in Chaco (N = 169, 75% females). We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA), dimethylarsinic acid (DMA)] in urine (U-As) using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR.

Results: Median U-As was 196 (5-95 percentile: 21-537) μg/L in Andes and 80 (5-95 percentile: 15-1637) μg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity) in Chaco (β = 0.027 per 100 μg/L, p = 0.0085; adjusted for age and sex), but not in Andes (β = 0.025, p = 0.24). U-As was also associated with longer telomere length in Chaco (β = 0.016, p = 0.0066) and Andes (β = 0.0075, p = 0.029). In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs.

Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

Keywords: AS3MT; MMA; cancer; energy; oxidative phosphorylation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Arsenic in urine is associated with higher copy number of mitochondrial DNA (log2-transformed, abbreviation mtDNAcn) and longer telomeres in blood. Scatter plots depicting relations between urinary arsenic (sum of inorganic arsenic metabolites) concentrations and log2-mtDNAcn and telomere length in Andes (A,B) and Chaco (C,D).
See this image and copyright information in PMC

References

    1. Ahmed S., Passos J. F., Birket M. J., Beckmann T., Brings S., Peters H., et al. . (2008). Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. J. Cell Sci. 121, 1046–1053. 10.1242/jcs.019372 - DOI - PubMed
    1. Ameer S. S., Engström K., Harari F., Concha G., Vahter M., Broberg K. (2015). The effects of arsenic exposure on blood pressure and early risk markers of cardiovascular disease: evidence for population differences. Environ. Res. 140, 32–36. 10.1016/j.envres.2015.03.010 - DOI - PubMed
    1. Antonelli R., Shao K., Thomas D. J., Sams R., II, Cowden J. (2014). AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. Environ. Res. 132, 156–167. 10.1016/j.envres.2014.03.012 - DOI - PubMed
    1. Bardach A. E., Ciapponi A., Soto N., Chaparro M. R., Calderon M., Briatore A., et al. . (2015). Epidemiology of chronic disease related to arsenic in Argentina: a systematic review. Sci. Total Environ. 538, 802–816. 10.1016/j.scitotenv.2015.08.070 - DOI - PubMed
    1. Blasco M. A. (2005). Telomeres and human disease: ageing, cancer and beyond. Nat. Rev. Genet. 6, 611–622. 10.1038/nrg1656 - DOI - PubMed