Arsenic induces telomerase expression and maintains telomere length in human cord blood cells

Ferrario, Daniele; Collotta, Angelo; Carfì, Maria; Bowe, Gerard; Vahter, Marie; Hartung, Thomas; Gribaldo, Laura

doi:10.1016/j.tox.2009.03.019

Cited by 60 publications

(47 citation statements)

References 67 publications

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“…We found in both study groups that arsenic was associated with longer telomeres in blood, even after taking cell profiles in blood into account. This confirms earlier findings (Ferrario et al, 2009) and provides strong evidence that arsenic has a true positive effect on telomeres. Arsenic causes lung cancer (International Agency for Reseasrch on Cancer, 2012), and our findings here suggests a mechanistic link that this occurs by lengthening of the telomeres.…”

Section: Discussionsupporting

confidence: 93%

“…This duality in response to mild vs. excessive oxidative stress might also explain previous findings on the effects of arsenic on telomere length. In human cord blood cells, sub-nM arsenite increased TERT (the main telomere-maintaining enzyme) gene and protein expression in vitro , resulting in maintained telomere length, while at 1 μM arsenite, TERT expression and telomere length decreased (Ferrario et al, 2009). In people exposed to arsenic via drinking water (1–1000 μg/L) in Inner Mongolia, TERT expression was positively associated with arsenic concentrations in water and in fingernails, and with the severity of arsenic related hyperkeratosis (Mo et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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

Ameer

Engström

et al. 2016

Front. Cell Dev. Biol.

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

Ameer

Engström

et al. 2016

Front. Cell Dev. Biol.

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“…An in vitro model suggests that female cord blood cells, in particular, are more sensitive than those of males to arsenic-induced telomerase stimulation at sub micro-molar concentrations (possibly due to the increased expression of ras and myc oncogenes) [28]. In mice, exposure to environmentally relevant doses of cadmium during gestation has been reported to affect thymocyte development of the newborn (< 12 h old) offspring [29], as well as to bring about persistent changes to T cell phenotypes and immune responses to a streptococcal vaccine, which were to some extent sex-specific [8].…”

Section: Discussionmentioning

confidence: 99%

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Nygaard

Palys

et al. 2017

PLoS ONE

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BackgroundArsenic and cadmium are environmental pollutants, and although the evidence for adverse immune effects after prenatal arsenic and cadmium exposures is increasing, little is known about the underlying immunological mechanisms.MethodsWe investigated the relationship between prenatal arsenic and cadmium exposures and a variety of T cell subpopulations measured in cord blood for 63 participants in the New Hampshire Birth Cohort Study. Post-partum toenail concentrations of arsenic and cadmium were used as an estimate of maternal exposure during pregnancy. The characteristics of cord blood proportions of T lymphocytes and subpopulations (expression of markers for Th1, Th2, Th17, Th1Th17, induced and natural regulatory T cells and NKTs) are presented.ResultsIn regression analyses, maternal arsenic exposure levels were inversely associated with cord blood T helper memory cells (-21%, 95% CI: -36%, -3%) and the association was found to be stronger in females. They were also inversely associated with activated T helper memory cells, particularly in males (-26%, 95% CI: -43%, -3%). Similarly, inverse associations were observed between cadmium exposure levels and activated T helper memory cells (-16%, 95% CI: -30%, -1%) and also for T helper memory cells in females (-20%, 95% CI: -35%, -3%).ConclusionThe results suggest that prenatal exposures to relatively low levels of arsenic and cadmium may contribute to altered distribution of T cell populations at birth. These changes in theory, could have contributed to the previously reported immunosuppressive effects observed later in infancy/childhood.

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“…In studies of cell lines (Zhang et al, 2003), animal models (Du et al, 2005), and human cells (Ferrario et al, 2009) high concentrations of As (>1 µM) have been observed to shorten telomeres and reduce cell survival. However, at lower levels (<1 µM), arsenic increases telomerase activity and maintains telomeres, promoting proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of cell lines (Zhang et al, 2003), animal models (Liu et al, 2003), and human cells (Ferrario et al, 2009) indicate that arsenic reduces telomere length at high concentrations (>1 µM), decreasing cell survival, but may increase telomerase activity and main telomere length at lower concentrations (<1 µM) (increasing survival). Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres in peripheral blood leukocytes (Chatterjee et al, 2014; Li et al, 2012) and increased expression of telomerase (Mo et al, 2009b), although few studies have addressed these research questions in human populations.…”

Section: Introductionmentioning

confidence: 99%

Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals

Gao

Roy

Lin

et al. 2015

Environmental Research

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Background Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water. Methods We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1,799 individuals. Association between arsenic exposure and a qPCR-based telomere length was assessed among 167 individuals. Results Urinary arsenic was possitively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P < 0.00035, Bonferroni correction threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction = 0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02). Discussion Our findings suggest that arsenic’s carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes.

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Arsenic induces telomerase expression and maintains telomere length in human cord blood cells

Cited by 60 publications

References 67 publications

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

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

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals

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