title: Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.
abstract: Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, F-69008 Lyon, France.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Lambert
authors.forename: Karin
authors.initials: K
authors.lastname: van Veldhoven
authors.forename: Christiana
authors.initials: C
authors.lastname: Demetriou
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
authors.forename: Kurt
authors.initials: K
authors.lastname: Straif
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wild
mesh_terms: D002273:Carcinogens / Q000145:classification / Q000302:isolation & purification / Q000633:toxicity; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D057890:Epigenomics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
chemical_list: D002273:Carcinogens; D006657:Histones