Co-Author: Emma C. Bowers, MS
Why should toxicologists and risk assessors care about epigenetics? According to Dana C. Dolinoy, PhD, University of Michigan School of Public Health, “many toxicologists may already be studying epigenetic phenomena — they just might not realize it.”
The epigenome is the master regulator of gene expression and, thus, has an integral role in nearly every physiological process. Therefore, toxicologists who research health, exposure-related disease, and susceptibility are actually concurrently studying the consequences of epigenetic regulation. While DNA and its 20,000 protein-coding genes can be thought of as static “hardware,” the epigenome is the “software” that coordinates its operation. Two of these mechanisms, DNA methylation and histone modification, regulate how readily genes encoded in the DNA can be expressed.
For 50 years, the fundamental principles and mechanisms of the epigenetic regulation of gene expression have been explored across myriad organisms and human diseases. While these advances laid the groundwork for understanding the “ins and outs” of the epigenome, the emergence of the new fields of toxicoepigenetics and environmental epigenetics has provided the opportunity to enhance our understanding of how chemical and non-chemical environments impact health and susceptibility. Founding literature in these fields has indicated that environmental exposure-induced changes to the epigenome can serve as both a mechanism of underlying exposure effects and a biomarker of both exposure and susceptibility. Furthermore, interactions between the environment and the epigenome may provide mechanistic insight into many toxicological phenomena that are not well-understood, such as non-genotoxic carcinogenesis, age-based windows of susceptibility, developmental reprogramming by early life exposures, and trans-generational exposure effects.
Epigenetics research has the potential to transform risk assessment, intervention, and mitigation strategies; however, these applications currently remain untapped. “In traditional risk assessment, we consider apical endpoints and apply safety factors to determine what would be an acceptable level of exposure. However, the path has yet to be defined to utilize toxicoepigenetics data in risk assessment,” explains SOT Regulatory and Safety Evaluation Specialty Section (RSESS) Vice President-Elect Marie Fortin, PhD, DABT, Rutgers. “Therefore, risk assessors and toxicoepigenetics researchers need to have a forum to meet, discuss, and collaborate in order to bridge this gap and leverage the full potential of the epigenome as a mechanism-based endpoint that can inform risk assessment.”
The last two SOT Annual Meetings have featured symposia, workshops, and continuing education courses on toxicoepigenetics, organized by SOT Molecular and Systems Biology Specialty Section (MSBSS) Vice President-Elect Shaun D. McCullough, PhD, US Environmental Protection Agency (US EPA) and University of North Carolina at Chapel Hill, and Dr. Dolinoy. Realizing the interest and enthusiasm of the toxicology community, but also the need for communication between specialties, they have developed the upcoming SOT Contemporary Concepts in Toxicology (CCT) meeting “Toxicoepigenetics: The Interface of Epigenetics and Risk Assessment,” being held November 2‒4, 2016, in Tysons, Virginia. “The goal of this meeting is to bring basic researchers and risk assessors together in the same room and to provide the venue for a collaborative discussion on how these two communities can work together to address critical questions in the field,” says Dr. McCullough.
Moving the field forward requires the concerted efforts of scientists with a broad range of interests and expertise, which is reflected by the meeting receiving collaborative endorsement from both RSESS and MSBSS. Further, in service to its mission to protect public health from the effects of pollution and to support the continued development of strong science as a basis for effective decision making, the US EPA is co-sponsoring the meeting. During the meeting, invited speakers will cover the role of the epigenome in mediating the effects of air pollution, heavy metal exposure, carcinogenesis, diet, and stress and will emphasize how these findings relate to risk assessment. The steering committee, comprised of individuals from academia, government, and industry, has been instrumental in ensuring the representation of major stakeholders in the field. “Our steering committee has been great,” says Dr. McCullough. “I can’t thank them enough!”
Drs. McCullough and Dolinoy also recognize that students are essential stakeholders in advancing toxicoepigenetics research. “We’re hoping to attract trainees to the meeting, as they will be adapting these findings into their work and leading the way in the future,” says Dr. Dolinoy. As such, the organizing committee has secured funding for five travel awards to bring trainees to the meeting. Each award comes with an invitation to speak at the conference and will cover the awardee’s travel, accommodation, and meeting registration. The meeting organizers also are coordinating a room-sharing program to help make attendance at the meeting more accessible for trainees.
Since epigenetics research can be applied to almost any aspect of toxicology, the organizers hope that toxicologists from all backgrounds will find the meeting informative. All are welcome to attend and take part in the discussion that will help shape these burgeoning fields as they continue to grow!