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

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.

Exploring telomere length in mother–newborn pairs in relation to exposure to multiple toxic metals and potential modifying effects by nutritional factors

“…In the present study, arsenic concentrations in both maternal blood, urine and placenta were positively associated with placental rTL. We have previously found positive associations between arsenic exposure and telomere length in blood of adults in the same Andean area [44, 45]. Similar findings were reported for adults in Bangladesh [46] and India [47] and among adolescents in Nepal [26].…”

Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study

“…In particular, the creatinine-corrected urine arsenic, cadmium and tungsten median concentrations in the SHS (1989-1991) were 8.9, 1.0 and 0.11 μg/g, respectively, and in the SHFS (2001-2004) were 4.3, 0.44 and 0.10 μg/g, respectively, while in NHANES data from 2004-2005 the median levels were 5.6, 0.17, 0.07 μg/g for ΣAs, Cd and W, respectively. Some epidemiologic studies have explored the association between arsenic exposure and telomere length, generally reporting positive associations (17)(18)(19)(20)(21)(22), i.e, increased arsenic exposure associated with longer telomeres. However, most of those studies are small and conducted in populations exposed to high levels of arsenic in drinking-water.…”

“…Most of the studies on the relationship between TL and arsenic have been conducted among populations affected by high arsenic exposure. In particular, small studies from Nepal (17), Argentina (18,19), Bangladesh (20), and India (21) suggested a positive association between arsenic and TL, while a study from Italy found a borderline inverse association (22). Cadmium exposure, however, has been consistently associated with shorter telomeres in Nepal (17) and NHANES 1999NHANES -2002.…”

Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number: a cross-sectional study

“…As described previously, SYBR Green-based real-time quantitative PCR (7900HT, Applied Biosystems, Foster City, CA, USA) was used to determine relative mtDNAcn and TL [ 32 ]. Master mixes for mtDNA and hemoglobin beta ( HBB ) gene runs were prepared with KAPA SYBR FAST qPCR Kit Master Mix (2X) ABI Prism (Kapa Biosystems, Woburn, MA, USA) and corresponding primers (0.20 μM for each primer) [ 33 , 34 ]. Master mixes for telomere runs were prepared with telomere primers (0.45 μM for each primer) [ 35 ], 1 × PCR Buffer (Thermo Fisher Scientific, Carlsbad, CA, USA), 1.75 mM MgCl 2 , 0.8 mM dNTPs, 0.3 mM SybrGreen (Thermo Fisher Scientific), 1 × Rox (Thermo Fisher Scientific), and 0.5 U Taq Platina (Thermo Fisher Scientific).…”