Mercury biomarkers and DNA methylation among michigan dental professionals

Abstract

Modification of the epigenome may be a mechanism underlying toxicity and disease following chemical exposure. Animal and human data suggest that mercury (Hg) impacts DNA methylation. We hypothesize that methylmercury and inorganic Hg exposures from fish consumption and dental amalgams, respectively, may be associated with altered DNA methylation at global repetitive elements (long interspersed elements, LINE-1) and candidate genes related to epigenetic processes (DNMT1) and protection against Hg toxicity (SEPW1, SEPP1). Dental professionals were recruited at Michigan Dental Association (MDA) meetings in 2009 and 2010. Subjects (n=131) provided survey data (e.g. exposure sources, demographics) and biological samples for Hg measurement and epigenetic analysis. Total Hg was quantified via atomic absorption spectrophotometry in hair and urine, indicative of methylmercury and inorganic Hg exposures, respectively. Global repetitive and candidate gene methylation was quantified via pyrosequencing of bisulfite converted DNA isolated from buccal mucosa. Hair Hg (geometric mean (95% CI): 0.37 (0.31–0.44) μg/g) and urine Hg (0.70 (0.60–0.83) μg/L) were associated with sources of exposure (fish consumption and dental amalgams, respectively). Multivariable linear regression revealed a trend of SEPP1 hypomethylation with increasing hair Hg levels, and this was significant (p<0.05) among males. The trend remained when excluding non-dentists. No significant relationships between urine Hg and DNA methylation were observed. Thus, in a limited cohort, we identified an association between methylmercury exposure and hypomethylation of a potentially labile region of the genome (SEPP1 promoter), and this relationship was gender specific.

Quality control and statistical modeling for environmental epigenetics: A study onin uterolead exposure and DNA methylation at birth

“…5,49,50 Sex-specific relationships between toxicant exposures and DNA methylation have been observed in animals 11 and humans. 7,9,51 In this study, LINE-1 was hypomethylated in girls compared to boys regardless of exposure (ANOVA P D 0.04, data not shown), a pattern previously observed in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort 5 and among adults. 50 Results following sex stratification suggested that DNA methylation in girls at LINE-1, IGF2, and HSD11B2 may be more sensitive to change following in utero Pb exposure, though sample size was small and significance marginal ( Table S6, Figs.…”

Genetic polymorphisms affecting susceptibility to mercury neurotoxicity in children: Summary findings from the Casa Pia Children's Amalgam Clinical Trial

“…Similarly, sex hormone regulation of BDNF signaling mediates sexually dimorphic axonal growth, resulting in generation of sex-specific neural circuits (Liu et al, 2012), also potentially underlying differences in response of boys and girls to Hg exposure (Spulber et al, 2010). Moreover, as noted above, epigenetic factors that differentially affect the timing, duration and magnitude of gene expression are also likely to contribute to the sex differences in susceptibility to Hg neurotoxicity observed (Jirtle and Skinner, 2007; Basu et al, 2013; Goodrich et al, 2013). In this regard, significant differences in DNA methylation patterns, methyl transferases, methyl binding proteins, and co-repressor proteins are currently recognized as contributing to the establishment and maintenance of sex differences in the brain and behavior (McCarthy et al, 2009), providing a plausible mechanistic basis for sex differences in response to Hg observed, both with respect to the numbers of genes and related neurologic processes affected as well as in the overall scope and direction of responses between boys and girls.…”

Effects of methylmercury on epigenetic markers in three model species: Mink, chicken and yellow perch

“…It has also been suggested that global DNA hypomethylation may be indicative of a generalized stress response, and that reduced DNA methylation is an early, adaptive and organized response to maintain genomic homeostasis (Szyf, 2011). Beyond global DNA methylation, MeHg exposure has been associated with both increased (Onishchenko et al, 2008; Hanna et al, 2012) and decreased (Gadhia et al, 2012; Goodrich et al, 2013) methylation of specific genes. A closer look at methylation status of individual genes may be necessary to uncover the toxicological consequences of MeHg induced DNA hypomethylation, and this may help increase understanding of the underlying mechanisms by which MeHg causes harm.…”

“…An in vitro study using mouse embryonic cells found that acute exposure to Hg 2+ impairs histone production and reduces H3-K27 methylation (Gadhia et al, 2012). Such epigenetic findings have been extended to humans as increased methylation of GSTM1/5 promoter in blood was associated with MeHg exposure in women undergoing in vitro fertilization (Hanna et al, 2012), and hypomethylation of SEPP1 was associated with hair Hg levels among a cohort of male dentists (Goodrich et al, 2013). Collectively these aforementioned studies provide founding evidence that mercury compounds can cause epigenetic changes.…”