Epigenetics and chemical safety assessment

LeBaron, Matthew J.; Rasoulpour, Reza J.; Klapacz, Joanna; Ellis-Hutchings, Robert G.; Hollnagel, Heli M.; Gollapudi, B. Bhaskar

doi:10.1016/j.mrrev.2010.04.003

Cited by 76 publications

(55 citation statements)

References 135 publications

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“…Epigenetic aberration is increasingly considered to play an important role in cellular response to environmental chemicals and induction of biologic consequences (36,37). Alterations in gene expression, DNA repair, genome stability, and malignant cell transformation could be the results of epigenetic modifications induced by environmental chemicals.…”

Section: Discussionmentioning

confidence: 99%

CpG Site–Specific Hypermethylation of p16INK4α in Peripheral Blood Lymphocytes of PAH-Exposed Workers

Yang

Zhang

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Sufficient epidemiologic evidence shows an etiologic link between polycyclic aromatic hydrocarbons (PAH) exposure and lung cancer risk. While the genetic modifications have been found in PAH-exposed population, it is unclear whether gene-specific methylation involves in the process of PAHassociated biologic consequence.Methods: Sixty-nine PAH-exposed workers and 59 control subjects were recruited. Using bisulfite sequencing, we examined the methylation status of p16INK4a promoter in peripheral blood lymphocytes (PBL) from

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Section: Discussionmentioning

confidence: 99%

CpG Site–Specific Hypermethylation of p16INK4α in Peripheral Blood Lymphocytes of PAH-Exposed Workers

Yang

Zhang

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…This has also been studied reasonably comprehensively and has been reviewed in detail recently (Zhang and Ho, 2011;LeBaron et al, 2010;Vandegehuchte and Janssen, 2011 …”

Section: Evidence For Endocrine Disruption Being Mediated By Epigenommentioning

confidence: 99%

“…The field of endocrine disruptor biology could benefit from carefully-designed analyses of the epigenome using these updated approaches, especially in human subjects, so it is worth describing some of the challenges involved in performing these studies stringently: -Study design: The fundamental principles guiding toxicology studies, including, e.g., relevant dose selection, route of administration, and duration of exposure, need to be taken into consideration in the design and interpretation of studies (LeBaron et al, 2010;Goodman et al, 2010). -Cell type: Epigenetic dysregulation events are believed to be somatic (occurring in a subset of cells in the body/organ) rather than constitutional (occurring in all cells of the body), requiring that the cell type mediating the phenotype be sampled.…”

Section: Issues To Address When Considering An Epigenomics Studymentioning

confidence: 99%

In vitro and in vivo testing methods of epigenomic endpoints for evaluating endocrine disruptors

Greally

Jacobs

2013

ALTEX

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SummaryDisclaimer: This paper is published under the sole responsibility of the authors and may not be considered as an EFSA output and is not intended to represent the views of EFSA. The paper is based on the annex of OECD (2012) The use of trade names is for identification only and does not constitute endorsement by the authors, EFSA, OECD, or the Albert Einstein College of Medicine. 1 Abbreviations BPA, bisphenol A; CG/CpG, cytosine-guanine dinucleotide; ChIP, chromatin immunoprecipitation; DNMT, DNA methyltransferase; ED, endocrine disruptor; EDTA-AG, OECD Endocrine Disruptor Testing and Assessment Advisory Group; ENCODE, ENCyclopedia Of DNA Elements; ES, embryonic stem; EZH2, enhancer of zeste homolog 2; IAP, intracisternal A particle; IUGR, intrauterine growth restriction; miRNA, micro RNA; MPS, massively-parallel sequencing; OECD, Organisation for Economic Cooperation and Development; TG, Test Guideline toxicology and safety assessment. At the research level, these efforts currently aim to elucidate the involvement of chemicalinduced epigenetic changes in adverse health effects, as well as to enable the exploitation of epigenetics particularly in the area of in vitro and in vivo modeling. While there have been plenty of reports linking endocrine disruptors with phenotypic abnormalities in wildlife, there are currently no publications describing epigenetic studies in wildlife undergoing these exposures.

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“…Clinical researchers are now considering epigenetic aberrations during carcinogenesis because DNA methyltransferase inhibitors are useful for cancer therapy (26)(27)(28). Thus, concern about chemically-induced epigenetic carcinogenesis in the next generation is increasing (6,8).…”

Section: Human Disease and Epigeneticsmentioning

confidence: 99%

“…Various environmental factors surrounding pregnant mothers and infants could be potential stimuli for epigenome alternation. For example, nutrient changes, exposure to environmental chemicals, and physical stresses such as insu‹cient care can alter the epigenome; thus, concern regarding chemicals that aŠect the health of the next generation has recently increased (6)(7)(8)(9). In this review, several studies conducted on animals are presented to summarize the evidence that the fetal and neonatal environment can in‰uence epigenomic modiˆcations retained in later stages of life.…”

Section: Introductionmentioning

confidence: 99%

Perinatal Exposure to Environmental Chemicals Induces Epigenomic Changes in Offspring

Ohsako

2011

Genes and Environment

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Many researchers propose that invisible internal alterations that occur through exposure to environmental factors during fetal or neonatal stages aŠect the risk of cancer, hypertension, and diabetes after maturation. Barker's hypothesis, which states that reduced fetal growth is strongly associated with metabolic syndromes including cardiovascular disease and diabetes, has now been widely accepted and expanded into the Developmental Origins of Health and Disease (DOHaD). Potential molecular mechanisms underlying this phenomenon include the alteration and persistence of epigenomic programming. Clear biochemical evidence has not yet been obtained in human studies; however, in laboratory animals, the fetal environment including physical and chemical factors altered epigenomic states such as DNA methylation and histone modiˆcation, and persistent changes aŠected speciˆc gene expression regulation, resulting in disease susceptibility. Furthermore, in recent studies, environmental chemical exposure during pregnancy altered sperm DNA methylation patterns of male oŠspring, and the altered status and resulting phenotypes were inherited in the next generation. Challenging and eccentric studies focusing on epigenetic transgenerational eŠects are currently being conducted to demonstrate the existence of Lamarckian inheritance.

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Epigenetics and chemical safety assessment

Cited by 76 publications

References 135 publications

CpG Site–Specific Hypermethylation of p16INK4α in Peripheral Blood Lymphocytes of PAH-Exposed Workers

CpG Site–Specific Hypermethylation of p16INK4α in Peripheral Blood Lymphocytes of PAH-Exposed Workers

In vitro and in vivo testing methods of epigenomic endpoints for evaluating endocrine disruptors

Perinatal Exposure to Environmental Chemicals Induces Epigenomic Changes in Offspring

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