Predicting Toxicity: Silent Spring Institute's High-throughput Screens for Chemicals Related to Breast Cancer
09:00 am US Eastern Time
Slides & Resources
Speaker presentation slides
Ruthann Rudel: Predicting Toxicity: Silent Spring Institute's High-throughput Screens for Chemicals Related to Breast Cancer
Dr. Yaswen: Understanding Breast Cancer Cells
Additional resources of interest
Review: Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation
Paper: In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis
Review: Improving the Human Hazard Characterization of Chemicals: A Tox21 Update
Silent Spring Institute: Tools for Green Chemistry: High-Throughput Screening
Silent Spring Institute: More information about high-throughput screening (a listing of other initiatives and resources)
Over 34 million tons of synthetic chemicals are produced or imported into the US every year, and hundreds of these chemicals are commonly found in women’s blood, urine, and breast tissue. While most have not been tested for their carcinogenic potential, among those that have, hundreds increase mammary tumors in laboratory animals. Animal tests, however, are both time- and resource-intensive, and they rarely evaluate the effects of chemical exposure during early life or prenatal development.
Recently, toxicologists have adopted high throughput screening in search of quick and accurate ways of predicting the toxicity of chemicals. However, so far these screens have relied primarily on human liver, kidney, and lung cells and therefore may say little about the effects of chemicals on breast cancer.
To fill that gap, Silent Spring Institute and their collaborators are designing high throughput toxicity screens using breast cells. The idea is to expose the cells to different chemicals and look for specific hallmarks of cancer such as DNA damage, increased estrogen receptor activity, or changes in the expression of genes involved in breast development and tumor growth. By comparing the effects of chemicals that are already known breast carcinogens with those that do not cause breast cancer, the scientists hope to identify molecular changes in the cells that predict increased breast cancer risk.
Not only will these novel screening tools dramatically quicken the pace of research on the role of chemicals in breast cancer, but also data derived from these screens could be used as basis for precautionary action. A comprehensive and publicly available list of suspect chemicals could help companies decide which chemicals to avoid or eliminate from their products and empower consumers to make smarter choices
Speakers discussed high-throughput toxicity screens on this CHE call.
Margaret L. Kripke, PhD, is Chief Scientific Officer of the Cancer Prevention and Research Institute of Texas. She is also Professor of Immunology and Vivian Smith Chair Emerita, at The University of Texas M.D. Anderson Cancer Center and Professor Emerita at the Graduate School for Biological Sciences in Houston. Dr. Kripke's research interests center on the immunology of the skin and skin cancer, how skin immune function is modified by exposure to ultraviolet light, and how the immune system influences the development of skin cancers. Dr. Kripke has authored more than 250 scientific publications and served on many peer review panels determining research funding. In 1993, Dr. Kripke served on a National Cancer Advisory Board Subcommittee to review the National Cancer Program. She served as President of the American Association for Cancer Research from 1993 to 1994 and President of the American Society for Photobiology from 1996 to 1997. She was a member of the Executive Committee of the Environmental Protection Agency’s Science Advisory Board, chaired the EPA Science Advisory Board Research Strategies Advisory Committee, and served on the United Nations Environment Program Subcommittee on Stratospheric Ozone Depletion. In 2000, she was elected as a Fellow of the American Association for the Advancement of Science. In 2003, she was appointed by President Bush as a member of the 3-person President’s Cancer Panel, a group that advises the President on the status and needs of the cancer problem in America and continued in this role through 2011. Dr. Kripke was appointed an inaugural member of the Academy of the American Association for Cancer Research in 2013. Currently, she sits on the Boards of Directors for three non-profit organizations, the Silent Spring Institute in Massachusetts, and Neighborhood Centers, Inc. and the Hermann Park Conservancy in Houston.
Ruthann Rudel, MS, is the Director of Research at Silent Spring Institute, and leads exposure and toxicology research programs focusing on endocrine active chemicals and on mechanisms by which chemicals may influence breast cancer risk. Her work in toxicology includes a review of early life exposure to chemicals that alter mammary gland development and implications for testing protocols and risk assessment, published in Environmental Health Perspectives. She also directed a major review of animal mammary gland carcinogens—published in Cancer in 2007—that compiled existing research on these carcinogens, reviewed key issues in study design and animal models, and synthesized information on exposure opportunities. She has published on toxicology and risk assessment for metals, indoor air pollutants, and endocrine disruptors. Her current research includes a project funded by the California Breast Cancer Research Program to transfer EPA's ToxCast cell culture assays into mammary tissue models and identify the assays that predict rodent mammary gland carcinogens.
Paul Yaswen, PhD, is a Staff Scientist at the Lawrence Berkeley National Laboratory and Principal Investigator of a California Breast Cancer Research Program-funded project to use cultured human breast cells to develop better ways to screen chemicals for cancer-causing effects. For nearly 3 decades, Dr. Yaswen has used such cells to study the cellular and molecular aberrations that lead to breast cancer. His group’s work has led to the identification and characterization of genes that, when active, promote (oncogenes) or suppress (tumor suppressor genes) cancer cell growth. The results of these studies, which may have implications for new preventative or therapeutic strategies, have been published in respected scientific journals. Along with researchers at the Silent Spring Institute, the University of Florida, and Stanford University, Yaswen’s group is currently using adult stem cells to form three-dimensional, gland-like structures called organoids that mimic the structure and function of real breast tissue, upon which chemicals can be tested for possible carcinogenicity.
The call was moderated by Sharyle Patton, Director of Commonweal's Biomonitoring Resource Center.