Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation

Herceg, Zdenko; Lambert, Marie-Pierre; Veldhoven, Karin van; Demetriou, Christiana A.; Víneis, Paolo; Smith, Martyn T.; Straif, Kurt; Wild, Christopher P.

doi:10.1093/carcin/bgt212

Cited by 91 publications

(80 citation statements)

References 241 publications

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“…Synchronous events occurring in this setting also include hypoxia, oxidative stress, apoptosis, mitophagy and autophagy [299][300][301][302] . Autophagy shows a double face in HCC.…”

Section: Resultsmentioning

confidence: 99%

Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson's disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem. Core tip: Hepatocellular carcinoma (HCC) is the fifth most common human cancer. This review summarizes current knowledge regarding the occupational risk factors of HCC. In particular, we underline not only the infective but also non-infective occupational risk exposure, including chemical agents and toxic metabolites which are a major cause of liver damage.

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“…Synchronous events occurring in this setting also include hypoxia, oxidative stress, apoptosis, mitophagy and autophagy [299][300][301][302] . Autophagy shows a double face in HCC.…”

Section: Resultsmentioning

confidence: 99%

Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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“…In addition to examples presented above, other evidence demonstrates that altering the DNA methylation status is one of the underlying mechanisms of the carcinogenicity of a number of established environmental and occupational carcinogenic agents, including benzene, metals, butadiene and pharmaceuticals (Hou et al, 2012;Kim et al, 2012;Pogribny and Beland, 2013;Brocato and Costa, 2013;Herceg et al, 2013).…”

Section: Other Environmental and Occupational Chemical Carcinogensmentioning

confidence: 96%

Alterations inDNAMethylation Resulting from Exposure to Chemical Carcinogens

Pogribny

Kobets

Beland

2014

Encyclopedia of Life Sciences

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Continuous exposure to natural and man‐made chemicals is a major cause of noncommunicable human diseases, including cancer. Accumulated data indicate that an exposure to chemical carcinogens induces a range of genetic and epigenetic events, including alterations in the deoxyribonucleic acid (DNA) methylation pattern, which may be associated with cancer development and progression. Accumulated evidence indicates that the response of the DNA methylome to chemical carcinogens, especially lifestyle and food carcinogens, is critical in the carcinogenic process. The better understanding of mechanisms and processes associated with carcinogen‐induced DNA methylation abnormalities may be helpful for carcinogen hazard identification, carcinogen risk assessment and management, and the prevention of cancer. Key Concepts: Exposure to natural and man‐made chemicals is a major cause of human cancer. Chemical carcinogens induce a range of genetic and epigenetic events, including alterations in the DNA methylation pattern. Alteration of the DNA methylation status is one of the underlying mechanisms of the carcinogenicity of a number of established environmental and occupational carcinogenic agents. Carcinogen‐induced DNA methylation changes consist of DNA and repetitive element demethylation, gene‐specific hypermethylation and gene silencing, gene‐specific hypomethylation and activation of gene transcription and altered expression or activity of DNA methyltransferases. Epigenetic alterations may be used as biomarkers in the evaluation of the carcinogenic potential of chemicals. The incorporation of epigenetic technologies in cancer risk assessment promises to enhance substantially the efficiency of carcinogenicity testing.

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“…Nevertheless, the epigenetic regulation of genes and, therefore, the plasticity of the epigenome play a key role in cancer development and progression (93,214). HDACs can act directly on chromatin, modifying histone acetylation and changing the characteristics of transcriptional factor recruitment on promoters.…”

Section: Hdacs and Sirtuins In Cancer: Quantitative And Functional Abmentioning

confidence: 99%

Targeting Histone Deacetylases in Diseases: Where Are We?

Benedetti

Conte

Altucci

2015

Antioxidants & Redox Signaling

102

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Significance: Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death. Recent Advances: Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, are currently being used in clinical trials for solid and hematological malignancies, and are, thus, promising candidates for cancer therapy. Critical Issues: (i) Non-specific (off-target) HDACi effects due to activities unassociated with HDAC inhibition. (ii) Advantages/disadvantages of non-selective or isoformdirected HDACi. (iii) Limited number of response-predictive biomarkers. (iv) Toxicity leading to dysfunction of critical biological processes. Future Directions: Selective HDACi could achieve enhanced clinical utility by reducing or eliminating the serious side effects associated with current first-generation non-selective HDACi. Isoform-selective and pan-HDACi candidates might benefit from the identification of biomarkers, enabling better patient stratification and prediction of response to treatment. Antioxid. Redox Signal. 23, 99-126.Shaping the Epigenome E pigenetic mechanism(s) allow genetically identical cells to adopt different phenotypes regulating transcriptional availability of the genome through differential chromatin marking and packaging (137), creating a network of mutually reinforcing or counteracting signals (192). A key aspect of epigenetics is that chromatin marks can be preserved and/or changed according to environmental, developmental, or pathological needs. These very complex and plastic steps are achieved via the activity of initiators (such as long noncoding RNA), writers (which establish the epigenetic mark, such as histone acetyltransferases), readers (which interpret the epi-mark), and erasers (which remove the epi-mark, such as histone deacetylases, or HDACs) (41, 232). In concert, remodelers (which reposition nucleosomes) and insulators (which build boundaries between epi-domains) create, maintain, and modulate the three-dimensional structure of networking within a cell (223). It is now clear that genetic and epigenetic mechanisms influence each other, cooperating to enable the acquisition of hallmarks of human cancer (89). The frequency of epi-target mutations seen in cancers underlines the relevance of mutations in epigenetic modifiers in cancer (213) and corroborates the concept that deregulation of epigenetic cont...

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Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation

Cited by 91 publications

References 241 publications

Hepatocellular carcinoma and the risk of occupational exposure

Hepatocellular carcinoma and the risk of occupational exposure

Alterations inDNAMethylation Resulting from Exposure to Chemical Carcinogens

Targeting Histone Deacetylases in Diseases: Where Are We?

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