Cited by 114Epigenetics and DNA MethylationToxic Organic Pollutants ImpactPesticide Exposure and Toxicity

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Effects of Mixtures of Polychlorinated Biphenyls, Methylmercury, and Organochlorine Pesticides on Hepatic DNA Methylation in Prepubertal Female Sprague-Dawley Rats

Desaulniers, Daniel, Xiao, Gong-hua, Lian, Hong, Feng, Yong-Lai, Zhu, Jiping, Nakai, Jamie, Bowers, Wayne J.·2009·International Journal of Toxicology

DOI 10.1177/1091581809337918

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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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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
ORCID: Desaulniers, Daniel
Lian, Hong
Feng, Yong-Lai
Zhu, Jiping
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
DOI: 10.1177/1091581809337918
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
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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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Effects of Mixtures of Polychlorinated Biphenyls, Methylmercury, and Organochlorine Pesticides on Hepatic DNA Methylation in Prepubertal Female Sprague-Dawley Rats

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