Genetic and carcinogenic effects of exposures on life forms across the biological spectrum were highlighted at the Genetics and Environmental Mutagenesis Society (GEMS) spring meeting. The event was held May 17 at the Research Triangle Park campus of the U.S. Environmental Protection Agency.

GEMS President-Elect Carol Swartz, D.V.M., Ph.D., lined up speakers who addressed topics ranging from improving on genetic toxicity tests that use bacterial cells, to the responses of different whale species exposed to the 2010 Deepwater Horizon oil spill.

“It’s always intrigued me that the genetic code is conserved enough across species that we can use everything from bacteria to whales to study processes that apply to humans,” Swartz said. She works for Integrated Laboratory Systems (ILS).

Black cohosh shows genotoxicity

Smith-Roe said that black cohosh has been marketed to women for relief of menopausal symptoms for more than a century. (Photo courtesy of Steve McCaw)

National Toxicology Program (NTP) genetic toxicologist Stephanie Smith-Roe, Ph.D., shared findings from NTP studies of black cohosh extract (BCE), a botanical dietary supplement marketed to women since the 1800s for menopausal symptoms such as hot flashes.

“NTP has been filling data gaps on botanicals for the last 20 years,” said Smith-Roe, referring listeners to an NTP fact sheet for more information. “BCE has been shown to be genotoxic in vivo and in vitro,” she summarized. “And we strongly suspect that it is due to disruption of the folate metabolism pathway.”

In response to a question from NIEHS Deputy Director Rick Woychik, Ph.D., Smith-Roe explained that NTP is now looking at developmental effects, and analyzing data from a clinical study of women who used BCEs. Scientists hope to learn how BCE affects folate and vitamin B12 levels, anemia, chromosomal damage, and more.

Insights on toxicity from cells, dogs, and whales

Swartz, right, thanked Recio and gave him a token of appreciation from GEMS. (Photo courtesy of Steve McCaw)

Toxicologist Leslie Recio, Ph.D., vice president for research and development and chief scientist at ILS, detailed the challenges of developing a new assay for drug testing and chemical risk assessment.

Recio and collaborator Bevin Engleward, Sc.D., from the Massachusetts Institute of Technology, combine scientific and engineering approaches with human liver cells, which are able to metabolize potential carcinogens. The aim of their work, funded by NIEHS, is to detect bulky DNA lesions that may be missed with available high-throughput technology.

“Getting [regulatory] acceptance of an alternative assay is one tough thing to do,” Recio said. He speaks from experience as a former member of an expert group for the Organisation on Economic Cooperation and Development, which is working to develop alternatives to safety tests that use animals (see related story on NTP efforts)

When dogs are canaries

Breen emphasized that laboratory animals are useful for learning about cancer progression but are less helpful for understanding the origins of spontaneous cancers. (Photo courtesy of Steve McCaw)

Matthew Breen, Ph.D., from North Carolina State University (NCSU), said dogs, especially those with registered pedigrees, can teach us a lot about cancers and the genes involved in them. This is due to their shorter lifespan and high degree of inbreeding.

Genetic analysis of cancer in purebred dogs can help researchers pinpoint key gene mutations, especially when littermates develop the same disease. Nature Medicine highlighted this work in a 2015 story.

Pets share much the same environment as their owners, said Breen, pointing to the home, its furnishings, water, and air. “Some of you may even feed your dogs people food,” he added. Breen, who is also a member of the NIEHS-funded NCSU Center for Human Health and the Environment, suggested that dogs might serve as canaries in the coal mine, to alert people to dangers in the environment.

Whales — our closest relative in the ocean

“Whales are our closest relatives in the ocean,” said Wise, who received the 2018 Career Achievement Award from the Society of Toxicology Metals Specialty Section. (Photo courtesy of Steve McCaw)

John Pierce Wise, Sr., Ph.D., from the University of Louisville, is interested in interactions among humans, wildlife, and ecosystems, which is an approach known as One Health (see related story). His talk focused on his work with whales, although he touched on studies of leatherback turtles and alligators as well.

Wise and his team tested whales in the Gulf of Mexico during and after the 2010 Deepwater Horizon oil spill. Focusing on chromium, which triggers DNA double strand breaks and inhibits repair, Wise said that whales appeared to be more resistant to its DNA damage.

“Chromium does not appear to inhibit [DNA] repair in whales, as it does in humans,” he said. Using cultured whale cells, Wise and his team hope to gain insights into human disease by uncovering the mechanisms involved in their resistance.

Citations:
Cora MC, Gwinn W, Wilson R, King D, Waidyanatha S, Kissling GE, Brar SS, Olivera D, Blystone C, Travlos G. 2017. A Black Cohosh Extract Causes Hematologic and Biochemical Changes Consistent with a Functional Cobalamin Deficiency in Female B6C3F1-N mice. Toxicol Pathol 45(5):614–623.

Rogers N. 2015. Canine clues: dog genomes explored in effort to bring human cancer to heel. Nat Med 21(12):1374–1375.

Schiffman JD, Breen M. 2015. Comparative oncology: what dogs and other species can teach us about humans with cancer. Philos Trans R Soc Lond B Biol Sci 370(1673).

Smith-Roe SL, Swartz CD, Shepard KG, Bryce SM, Dertinger SD, Waidyanatha S, Kissling GE, Auerbach SS, Witt KL. 2018. Black cohosh extracts and powders induce micronuclei, a biomarker of genetic damage, in human cells. Environ Mol Mutagen doi:10.1002/em.22182 [Online 18 Apr 2018].

Wise JP Jr, Wise JT, Wise CF, Wise SS, Gianios C Jr, Xie H, Thompson WD, Perkins C, Falank C, Wise JP Sr. 2014 Concentrations of the genotoxic metals, chromium and nickel, in whales, tar balls, oil slicks, and released oil from the Gulf of Mexico in the immediate aftermath of the deepwater horizon oil crisis: is genotoxic metal exposure part of the Deepwater Horizon legacy? Environ Sci Technol 48(5):2997−3006.