Leading researchers across the spectrum of toxicology gathered at the NIEHS on 15 October 2002 for an in-depth roundtable discussion on the biology of sex differences in environmental health. Cosponsored by the NIEHS and the Society for Women's Health Research, an advocacy group located in Washington, D.C., the one-day conference examined how sex interacts with environmental exposures to yield sometimes-different health effects in men and women.
A primary goal of the conference was to outline how a person's sex influences his or her environmental health--teasing out how biological and societal differences in men's and women's lives impact their health. "Environmental health lies right in the middle of the great tangled hairball of research," says Sherry Marts, the society's scientific director. "Sex is a crucial biological variable that needs to be looked at at all levels and in all organ systems. Sex matters."
The conference was one of a series sponsored by the society to help establish an agenda for understanding the influence of sex and gender across the life sciences. The series expands on a 2001 Institute of Medicine report, Exploring the Biological Contributions to Human Health: Does Sex Matter?, which the society helped initiate and sponsor. Other series roundtables have addressed sex differences in cardiovascular health and disease, immunity and autoimmunity, and prenatal development. "We want to encourage that sex differences be part of research, all research, integrated into everything," explains society president Phyllis Greenberger.
Understanding Sex Differences
The first half of the October roundtable focused on traditional and newly developed scientific tools and how they can enhance understanding of sex-specific responses to environmental exposures. James Huff, an NIEHS senior investigator, discussed bioassays in chemical carcinogenesis. The picture is complicated. "Roughly half the chemicals we test have a tumor effect at one site in one sex in one species," Huff reported. Many cancer differences in animal bioassays, he said, likely reflect differences in the sex-hormonal biological context as it may be impacted by environmental exposures.
Although highly effective in developing preventive health strategies, animal-based bioassays also have weaknesses, especially the time and animal facility costs involved in whole-organism work. Expanding these assays to cover effects in both sexes would increase costs further by increasing the number of animals involved. However, these bioassays clearly signal sex differences in response to environmental exposures, and have led to better biologic understanding of such differences.
Mary Jane Cunningham, director of discoveries at Molecular Mining Corporation, a Kingston, Ontario-based data analysis and predictive modeling technology company, discussed methods that may overcome those barriers. She described gene expression microarrays and advanced data mining and analysis methods allowing rapid detection and comparison of the effects of environmental exposures. "It takes only three to four days to obtain the expression of ten thousand or more genes using arrays, and only a matter of minutes to analyze the data," she said. "These technologies are available now. However, when the cost of the arrays is reduced or [they] become more efficient, you can afford to allow for testing of both sexes." (Others are not so optimistic, however, and believe that microarray technologies will take enormous funding, resources, and time to develop and validate.)
Kent Hunter, an investigator at the National Cancer Institute, described work using quantitative trait genetics, a breeding approach that untangles processes controlled by multiple genes to elucidate how environmental factors can affect development of sex-specific cancers. He has found that how individuals differ in one trait--expression of the tumor suppressor Atm--may help determine whether breast cancer stays dormant or metastasizes. …