Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.

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 di...

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Main Authors: Syeda Shegufta Ameer, Yiyi Xu, Karin Engström, Huiqi Li, Pia Tallving, Barbro Nermell, Analia Boemo, Lidia Guadalupe Peñaloza, Luis A. Parada, Gabriela Concha, Florencia Harari, Marie Vahter, Karin Broberg
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-08-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:http://journal.frontiersin.org/Journal/10.3389/fcell.2016.00087/full
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author Syeda Shegufta Ameer
Yiyi Xu
Karin Engström
Huiqi Li
Pia Tallving
Barbro Nermell
Analia Boemo
Lidia Guadalupe Peñaloza
Luis A. Parada
Gabriela Concha
Florencia Harari
Marie Vahter
Karin Broberg
author_facet Syeda Shegufta Ameer
Yiyi Xu
Karin Engström
Huiqi Li
Pia Tallving
Barbro Nermell
Analia Boemo
Lidia Guadalupe Peñaloza
Luis A. Parada
Gabriela Concha
Florencia Harari
Marie Vahter
Karin Broberg
author_sort Syeda Shegufta Ameer
collection DOAJ
description 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.
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spelling doaj.art-86a7705405864cc0ac1f40d1ce9d33132022-12-21T18:03:42ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2016-08-01410.3389/fcell.2016.00087196830Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.Syeda Shegufta Ameer0Yiyi Xu1Karin Engström2Huiqi Li3Pia Tallving4Barbro Nermell5Analia Boemo6Lidia Guadalupe Peñaloza7Luis A. Parada8Gabriela Concha9Florencia Harari10Marie Vahter11Karin Broberg12Lund UniversityLund UniversityKarolinska InstitutetLund UniversityLund UniversityKarolinska InstitutetUniversidad Nacional de SaltaUniversidad Nacional de SaltaUNSa - CONICETNational Food AgencyKarolinska InstitutetKarolinska InstitutetKarolinska InstitutetBackground: 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.http://journal.frontiersin.org/Journal/10.3389/fcell.2016.00087/fullOxidative PhosphorylationCancerEnergyMMAAs3MT
spellingShingle Syeda Shegufta Ameer
Yiyi Xu
Karin Engström
Huiqi Li
Pia Tallving
Barbro Nermell
Analia Boemo
Lidia Guadalupe Peñaloza
Luis A. Parada
Gabriela Concha
Florencia Harari
Marie Vahter
Karin Broberg
Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
Frontiers in Cell and Developmental Biology
Oxidative Phosphorylation
Cancer
Energy
MMA
As3MT
title Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
title_full Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
title_fullStr Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
title_full_unstemmed Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
title_short Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.
title_sort exposure to inorganic arsenic is associated with increased mitochondrial dna copy number and longer telomere length in peripheral blood
topic Oxidative Phosphorylation
Cancer
Energy
MMA
As3MT
url http://journal.frontiersin.org/Journal/10.3389/fcell.2016.00087/full
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