Table 2.
Summary of studies of environmental toxicants with epigenetic alterations in human subjects.
| Reference | Year | Environmental toxicants | Subjects | Findings |
|---|---|---|---|---|
| Smoking | ||||
| Maccani et al. [166] | 2010 | Maternal cigarette smoking | 25 human placentas | Downregulation of miR-16, miR-21, and miR-146a |
| Toledo-Rodriguez et al. [158] | 2010 | Maternal cigarette smoking | 156 adolescents | Hypermethylation at promoter 6 of BDNF gene and 5′ UTR |
| Flom et al. [161] | 2011 | Prenatal tobacco smoke | 90 women | Demethylation at Sat2 repetitive elements |
| Suter et al. [159] | 2011 | Maternal smoking | 36 placental samples | Changes in genome wide placental DNA methylation |
| Novakovic et al. [164] | 2014 | Maternal smoking | Cord blood mononuclear cells, buccal epithelia, and placentas |
Induced hypomethylation at aryl hydrocarbon receptor repressor (AHRR) gene with differences between tissue and maintenance at 18 months of age |
| Stroud et al. [160] | 2016 | Maternal smoking during pregnancy |
45 mother-infant pairs age 18–35 | Demethylation at CpG3 and CpG4 of placental NR3C1 promoter revealed that monozygotic twins are generally more similar in their DNA methylation level than dizygotic twins |
|
| ||||
| BPA and phthalates | ||||
| Avissar-Whiting et al. [177] | 2010 | BPA treatment | Placental cell lines 3A, TCL-1, and HTR-8 |
Increase miR-146a |
| Kundakovic et al. [172] | 2013 | In utero BPA exposure | Cord blood samples | Sex-specific (males) hypermethylation at BDNF promoter IV |
| Faulk et al. [174] | 2016 | Perinatal BPA exposure | Human and mouse liver samples | Hypomethylation at LINE-1 repetitive element in human and mouse |
| LaRocca et al. [178] | 2016 | Prenatal phthalates exposure | Placentas | Decrease in miR-185 expression |
|
| ||||
| POPs | ||||
| Rusiecki et al. [181] | 2008 | Plasma POP concentration | Blood DNA of 70 Greenlandic Inuit | Increasing serum levels of POPs have a strong correlation with global DNA hypomethylation as assessed by Alu repetitive element |
| Kim et al. [182] | 2010 | Lipid-standardized concentrations of POPs |
Blood DNA of 86 healthy Koreans | Decrease DNA methylation in the Alu sequence correlate with increase concentration of POPs |
| Mitchell et al. [185] | 2012 | Polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) in human postmortem brain |
Human postmortem brain | PCB 95 was detected in 5/6 Dup15q postmortem brain and may be related to hypomethylation of LINE-1 repetitive elements |
| Lind et al. [184] | 2013 | Lipid-standardized concentrations of POPs |
524 70-year-old Swedish | Global DNA hypermethylation is associated with high levels of POPs |
| Itoh et al. [183] | 2014 | Serum organochlorine level | Leukocyte DNA of 399 Japanese | Inverse association between global DNA methylation and serum organochlorine level |
| Heavy metals | ||||
| Kovatsi et al. [189] | 2009 | Lead blood concentration | 19 individuals (10 control and 9 exposed) |
p16 promoter was partially methylated under low exposure of lead and was fully methylated under high exposure of lead |
| Pilsner et al. [190] | 2009 | Prenatal lead exposure | 103 umbilical cord blood | Maternal lead exposure was associated with hypomethylation of Alu and LINE-1 repetitive elements |
| Senut et al. [192] | 2014 | Lead | Human embryonic stem cells and hESC-derived neurons |
Global DNA methylation changes in differentiating hESCs both hyper- and hypomethylated |