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Effects of Mixtures of Polychlorinated Biphenyls, Methylmercury, and Organochlorine Pesticides on Hepatic DNA Methylation in Prepubertal Female Sprague-Dawley Rats
Abstract
DNA methylation is one of the epigenetic mechanisms that regulates gene expression, chromosome structure, and stability. Our objective was to determine whether the DNA methylation system could be a target following in utero and postnatal exposure to human blood contaminants. Pregnant rats were dosed daily from gestation day 1 until postnatal day 21 with 2 dose levels of either organochlorine pesticides (OCP; 0.019 or 1.9 mg/kg/day), methylmercury chloride (MeHg; 0.02 or 2 mg/kg/day), polychlorinated biphenyls (PCBs; 0.011 or 1.1 mg/kg/day), or a mixture (Mix; 0.05, or 5 mg/kg/day) including all 3 groups of chemicals. Livers from 1 female offspring per litter were collected at postnatal day 29. Hepatic analysis revealed that the mRNA abundance for DNA methyltransferase (DNMT)-1, -3a, and -3b were significantly reduced by the high dose of PCB, that the high dose of MeHg also reduced mRNA levels for DNMT-1, and -3b, but that OCP had no significant effects compared with control. The high dose of PCB and Mix reduced the abundance of the universal methyl donor S-adenosylmethionine, and Mix also reduced global genome DNA methylation (5-methyl-deoxycytidine/5-methyl-deoxycytidine + deoxycytidine). The latter is consistent with pyrosequencing methylation analysis, revealing that the high-dose groups (except OCP) generally decreased the methylation of CpG sites (position -63 to -29) in the promoter of the tumor suppressor gene p16 INK4a . Overall, these hepatic results suggest that the DNA methylation system can be affected by exposure to high doses of blood contaminants, and that OCP is the least potent chemical group from the investigated mixtures.
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“In utero and lactational exposure to a mixture of 14 NDL + DL PCBs at 1.1 mg/kg/day from GD1 to postnatal day (P) 21 reduced levels of the methyl donor S-adenosylmethionine as well as levels of Dnmt1 , 3a, and 3b to 4, 54, and 17 of control values, respectively, in liver of prepubertal female Sprague-Dawley rats [ 32 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [32]
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Metadata
- Authors
- Desaulniers, D., Xiao, G.-H., Lian, H., Feng, Y.-L., Zhu, J., Nakai, J., & Bowers, W. J.
- Affiliations
- Health Canada (CA)
- Corresponding author
- Desaulniers, Daniel
- Venue
- International Journal of Toxicology
- Publisher
- SAGE Publications
- Published
- 2009-07
- Volume
- 28
- Issue
- 4
- Pages
- 294-307
- ISSN
- 1091-5818 (ISSN-L)
- 1092-874X
- OpenAlex
- W2133372930
- Cited by
- 114
- References
- 80
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 6 · 2013: 12 · 2012: 14
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pesticide Exposure and Toxicity
- Keywords
- polychlorinated biphenyls, methylmercury, organochlorine pesticides, chemical mixtures, DNA methylation, S-adenosylmethionine, global DNA methylation, CpG methylation, prenatal exposure, liver, epigenetic toxicity
- MeSH terms
- Animals, Base Sequence, Chromatography, Liquid, Dose-Response Relationship, Drug, Female, Hydrocarbons, Chlorinated, Liver, Methylmercury Compounds, Pesticides, Polychlorinated Biphenyls, Pregnancy, Sexual Maturation, Spectrophotometry, Ultraviolet, DNA Primers, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Spectrometry, Mass, Electrospray Ionization, Rats
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