Environmental Factor, October 2011, National Institute of Environmental Health Sciences
Women scientists shine at NCSOT meeting
Dodd, who is senior toxicologist at The Hamner Institutes, introduced the program, noting proudly that NCSOT is the largest regional chapter of SOT with 373 members, 106 of them postdocs and students. He also announced the upcoming spring meeting and poster session to be held at EPA Feb. 23. (Photo courtesy of Steve McCaw)
Dodd congratulated this year's PARC winners on the prizes and announced cash awards from NCSOT sponsors. Shown, left to right, are Kurtz, first prize and $500 from Charles River Laboratories; EPA postdoc Nicole Kleinstreuer, Ph.D., second prize and $250 from VWR International; NIEHS/NTP postdoc Yang Sun, Ph.D., third place and $100 from VWR International; and Dodd. (Photo courtesy of Steve McCaw)
Hughes, a scientist with EPA, created an integrated agenda on epigenetics that segued smoothly from leading-edge exploratory research into the questions about regulation that arise as a response to the findings. (Photo courtesy of Steve McCaw)
Former NCSOT student winner Dolinoy's ties to the Triangle area go back to her time as a graduate student at Duke University and postdoctoral fellow in the lab of Randy Jirtle, Ph.D.(http://www.geneimprint.com/lab/) (Photo courtesy of Steve McCaw)
This fall's North Carolina Chapter of the Society of Toxicology (NCSOT) meeting at NIEHS Sept. 22, as usual, showcased the talents of trainees and keynote talks by three invited speakers. But what made this meeting stand out was its domination by women scientists.
Chaired by NC SOT President Darol Dodd, Ph.D., the meeting opened with presentation of the group's President's Award for Research Competition (PARC) to three area postdoctoral fellows, all young women, and a talk by first-place winner Lisa Kurtz, Ph.D., a postdoctoral fellow at The Hamner-University of North Carolina (UNC) Institute for Drug Safety Sciences.
Kurtz presented findings from a study of genes differentially expressed by a genetically diverse population of 34 strains of mice, with the goal of ultimately predicting which patients treated with the powerful tuberculosis drug isoniazid might develop liver toxicity. Her group is especially concerned about the small minority who progress to hepatitis and the approximately one percent who develop potentially fatal drug-induced liver injury.
The main program, designed by NCSOT Vice-president Mike Hughes, Ph.D., focused on new discoveries about the role of epigenetic alterations in environmental health by two NIEHS Outstanding New Environmental Scientist (ONES)(https://factor.niehs.nih.gov/2011/august/science-ones/index.cfm) awardees, followed by a consideration of issues regulators could face as they incorporate this new science into evaluation of safety and risk.
“Environmental Epigenetics: From Mice to Men”
Leading off the program of keynote speakers was University of Michigan geneticist Dana Dolinoy, Ph.D., who presented an introduction to and brief history of research into epigenetic modifications, the potentially heritable changes in gene expression that occur without changes in DNA itself. Dolinoy described experiments with Agouti mice exposed to levels of bisphenol-A (BPA) that altered coat color, body composition, and susceptibility to disease.
Dolinoy has expanded her research strategy with whole genome next-generation deep sequencing in animals to discover links between epigenetic changes and adverse phenotype in experiments with various doses of BPA, by itself and in mixture with phthalates.
Referring to her more recent work with human clinical samples, Dolinoy talked briefly about new population-based studies with a Mexico City birth cohort and with a cohort of urban and rural girls in Egypt. Despite exciting new findings from epigenetic studies by her group and others, Dolinoy conceded, “We're still in the infancy of this field.”
“Arsenic and the Epigenome”
Expanding on the theme of giving epigenetics a very human face, UNC toxicologist Rebecca Fry, Ph.D.(http://www.sph.unc.edu/?option=com_profiles&Itemid=1891&profileAction=ProfDetail&pid=714233563) , began her talk close to home with a reference to her recent survey of wells that provide water to 2.3 million people in North Carolina. The survey found levels of iAS as high as 196 parts per billion (ppb) in the most highly contaminated wells - nearly 20 times the so-called safe level of 10 ppb(https://water.epa.gov/lawsregs/rulesregs/sdwa/arsenic/index.cfm) established by the World Health Organization and U.S. Environmental Protection Agency (EPA).
Fry reported on her work with a cohort of residents of Zimapan, Mexico exposed to levels of inorganic arsenic (iAs) as high as 1,000 ppb in their drinking water. With a cohort of infants, Fry is investigating how gestational exposure to arsenic alters newborn expression of genes, particularly those involved in tumor suppression, along the NF-kB inflammatory response pathway, how this modulation is influenced by newborn genetics and epigenetics, and how gestational exposure to iAs influences risk for developing cancer, diabetes, and cardiovascular disease in adulthood.
Questions about regulation in regard to epigenetic effects
The final speaker of the day, veterinary pathologist Doug Wolf, D.V.M., Ph.D., admitted as he began his talk that he had far more questions than answers to offer about epigenetics from his perspective as a regulatory scientist with the EPA. Wolf reviewed the regulatory scheme for making decisions about mutagenic chemicals and speculated about how that framework might deal with chemicals that trigger epigenetic changes.
“Epigenetics is kind of in this gray zone [of regulatory status],” he said. “Variability issues make this more complicated [because] of age- and diet-dependent differences among affected individuals.”