Epigenomic biomonitors: global DNA Hypomethylation as A Biodosimeter of Life-Long Environmental Exposures

Guerrero-Preston, Rafael; Herbstman, Julie; Goldman, Lynn R.

doi:10.2217/epi.10.77

Cited by 16 publications

(15 citation statements)

References 21 publications

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“…For head and neck cancer, saliva and oral rinse have been used to obtain DNA from the oral epithelium to analyze the DNA hypermethylation profile [ 101 , 108 ] Among potential biomarkers for oral carcinogenesis, HOXA9 (Homeobox A9) and NID2 (Nidogen 2) hold high promise due to their apparent sensitivity and specificity. Additional methylated genes, such as HS3ST2 , NPY , EYA4 , WT1 , and the combination of E-cadherin , TMEFF2 , and MGMT methylations, could also serve as potential biomarkers for early detection of HNSCC [ 78 , 99 , 107 ]. CHFR (i.e., Checkpoint with FHA and RING finger domains) hypermethylation is a late event in HNSCC, suggesting an association with tumor progression and potential use as a biomarker of late stage disease progression [ 99 ].…”

Section: Epigenetic Modifications Associated With Tumor Progressiomentioning

confidence: 99%

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Castilho

Squarize

Almeida

2017

IJMS

136

121

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Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs), a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.

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Section: Epigenetic Modifications Associated With Tumor Progressiomentioning

confidence: 99%

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Castilho

Squarize

Almeida

2017

IJMS

136

121

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“…Similar to locus-specific DNA methylation changes, global DNA methylation changes also represent a biodosimeter of lifelong environmental exposures [35]. The consequence of PEMCS for global methylation was addressed by Wilhelm-Benartzi et al, who in placenta tissue examined both gene-associated loci and long interspersed nuclear element - 1 ( LINE - 1 ) and AluYb8 repetitive elements [36].…”

Section: Introductionmentioning

confidence: 99%

Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking

Larsen

Bilde

et al. 2016

Clin Epigenet

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AimsMaternal cigarette smoking during pregnancy increases the risk of negative health consequences for the exposed child. Epigenetic mechanisms constitute a likely link between the prenatal exposure to maternal cigarette smoking and the increased risk in later life for diverse pathologies. Maternal smoking induces gene-specific DNA methylation alterations as well as global DNA hypermethylation in the term placentas and hypomethylation in the cord blood. Early pregnancy represents a developmental time where the fetal epigenome is remodeled and accordingly can be expected to be highly prone to exposures with an epigenetic impact. We have assessed the influence of maternal cigarette smoking during the first trimester for fetal global DNA methylation.Methods and resultsWe analyzed the human fetal intestines and livers as well as the placentas from the first trimester pregnancies. Global DNA methylation levels were quantified with ELISA using a methylcytosine antibody as well as with the bisulfite pyrosequencing of surrogate markers for global methylation status, LINE-1, and AluYb8. We identified gender-specific differences in global DNA methylation levels, but no significant DNA methylation changes in exposure responses to the first trimester maternal cigarette smoking.ConclusionsAcknowledging that only examining subsets of global DNA methylation markers and fetal sample availability represents possible limitations for the analyses, our presented results indicate that the first trimester maternal cigarette smoking is not manifested in immediate aberrations of fetal global DNA methylation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0296-0) contains supplementary material, which is available to authorized users.

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“…Adverse environmental conditions -such as exposure to cytotoxic agents -may also result in epigenetic changes (Laurent et al, 2010) likely associated with proliferative blocks, which can arise during intrauterine life and persist from birth to death (Guerrero-Preston et al, 2011). Of note, we observed that the hypermethylation induced by PCBs in fetal cells is not reversible by interrupting the exposure to A1254.…”

Section: Discussionmentioning

confidence: 63%

Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure

Anzalone

Sampino

Czernik

et al. 2018

Toxicology in Vitro

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A B S T R A C TPolychlorinated biphenyls (PCBs) are persistent organic pollutants ubiquitously detectable in the environment and in the food chain. Prenatal exposure to PCBs negatively affects fetal development and produces long-term detrimental effects on child health. The present study sought to evaluate the cytotoxic and genotoxic effects of chronic PCB exposure on fetal cells during pregnancy. To this aim, sheep embryonic fibroblasts (SEF) and amniocytes (SA) were cultured in vitro in the presence of low doses of PCBs for a period of 120 days, comparable to the full term of ovine pregnancy. Cellular proliferation rates, global DNA methylation, chromosome integrity, and markers of DNA damage were evaluated at different time points. Moreover, SEF treated with PCBs for 60 days were left untreated for one further month and then examined in order to evaluate the reversibility of PCB-induced epigenetic defects. PCB-treated SEF were more sensitive than SA treated with PCBs, in terms of low cell proliferation, and increased DNA damage and global DNA methylation, which were still detectable after interruption of PCB treatment. These data indicate that chronic exposure of fetal cells to PCBs causes permanent genomic and epigenetic instability, which may influence both prenatal and post-natal growth up to adulthood. Our in vitro model offer a simple and controlled means of studying the effects of different contaminants on fetal cells -one that could set the stage for targeted in vivo studies.

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Epigenomic biomonitors: global DNA Hypomethylation as A Biodosimeter of Life-Long Environmental Exposures

Cited by 16 publications

References 21 publications

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking

Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure

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