Genetic and Molecular Ecotoxicology: A Research Framework Susan Anderson,1 Walter Sadinski,1 Lee Shugart,2 Peter Brussard,3 Michael Depledge,4 Tim Ford,5 JoEllen Hose,6 John Stegeman,7 William Suk,8 Isaac Wirgin,9 and Gerald Wogan0 1Lawrence Berkeley Laboratory, Berkeley, California; 2Oak Ridge National Laboratory, Oak Ridge, Tennessee; 3University of Nevada Reno, Reno, Nevada; 4University of Plymouth, Plymouth, UK; 5Harvard University, Cambridge, Massachusetts; 6 CCidental College, Los Angeles, California; 7Woods Hole Oceanographic Institute, Woods Hole, Massachusetts; 8National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; 9New York University Medical Center, Tuxedo, New York; 10Massachusetts Institute of Technology, Cambridge, Massachusetts Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of important concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics, there was general agreement that there are substantive new opportuni- ties to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosys- tem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. - Environ Health Perspect 102(Suppl 12):3-8 (1994) Key words: genetic, molecular, ecotoxicology, biomarkers, genotypes, genotoxic, global pollution, populations, ecosystems, biodiversity, hazardous substances Introduction informative diagnostic and prognostic Definition techniques available. Second, interest in The Napa Conference on Genetic and the preservation of biodiversity has height- We propose that genetic ecotoxicology Molecular Ecotoxicology provided an ened concerns that effects of hazardous may best be defined as: opportunity to assess the field of genetic substances on genetic variability are not "The study of chemical- or radiation- and molecular ecotoxicology in light of well understood. Third, there has been induced changes in the genetic material of important recent developments. First, there rapid advancement of new molecular natural biota. Changes may be direct alter- is a growing sense of urgency regarding approaches for analysis of gene structure ations in genes and gene expression or global pollution, which challenges us to and function as well as improved validation selective effects of pollutants on gene fre- assess subtle sublethal effects with the most of more classical techniques such as cytoge- quencies." netic analyses. These developments set the Thus, this definition attempts to stage for new research emphasizing broad encompass direct DNA damage, epigenetic This article synthesizes findings of the Napa goals and applications across levels of bio- effects, and changes in gene pools attribut- Conference on Genetic and Molecular Ecotoxicology logical organization. Thus, these concepts able to toxicant exposure. In the past, held 12-15 October 1993 in Yountville, California. must be integrated into a more compre- genetic ecotoxicology has been identified This conference was supported primarily by the National Institute of Environmental Health Sciences hensive, contemporary definition of genetic primarily with the study of direct DNA (NIEHS) Superfund Basic Research Program (W. Suk, ecotoxicology. damage. Semantic problems could stem Program Director). Additional support was provided The goals of this article are to identify a from efforts to expand the definition of NIEHS by the University of California, Berkeley, a response to embrace many sorts Superfund Program Project (M. Smith, Principal more inclusive identity and modern genotoxic Investigator, S. Neal, Project Administrator) and by an framework for future research in genetic and of molecular change. Therefore, we antici- award from the Pew Scholars in Conservation and molecular ecotoxicology. We present the pate that the proposed definition will serve the Environment (S. Anderson, Principal Investigator). consensus of the group at the Napa as a focus for future debate. Only recently We are indebted to the many participants in the con- ference whose voices are expressed throughout this Conference, but also highlight the diversity have attempts been made to place the con- review. of opinion on key topics. We present the sequences of "pollutant-induced changes in Address correspondence to Dr. Susan Anderson, following: a proposed definition of the field, genetic material" in a broader, more envi- Bldg. 70-193A, Lawrence Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA 94708. Telephone its potential relevance, key goals, core chal- ronmentally relevant context (1). (510) 486-4654. Fax (510) 486-5401. lenges, and a framework for future research. Environmental Health Perspectives 3 ANDERSON ETAL. Relevance potentially some of the most important ardous substances in the environment. Hazardous substances are distributed widely sublethal impacts of exposure to genotoxic Biomarkers alone could be used to provide in ecosystems due to diverse human activi- substances (8). As the state of the art of historical information on individuals and ties such as energy usage, industrial enter- research in ecotoxicology advances, we populations affected by hazardous exposure, prises, agriculture, and activities of the hopefully will be able to document more identify species at risk due to exposure, defense industry. The long-term ecological such effects and improve our capabilities to derive cleanup targets for site remediation, effects of these substances, as well as effects predict effects on populations. assess effects ofcontaminants on the genetic of increasing ultraviolet-B (UV-B) radiation Examples of changes in gene pools diversity of populations, and measure as a consequence of ozone depletion, are attributable to pollutant exposure are avail- effects in sentinel species as potential indi- largely unknown. For example, ecosystem able in an underappreciated, diverse litera- cators of human exposure to chemicals pre- protection is based largely on assessments of ture. Well-known examples, such as those sent at Superfund sites. lethality in model organisms rather than on of industrial melanism, pesticide tolerance, an understanding of toxic effects in situ on and tolerance to metals in numerous organ- Goals and Challenges natural populations. Similarly, damage isms have been reviewed (9). Recently We propose that the overall goal of genetic assessments ofcatastrophic events such as oil attention has been directed toward the ecotoxicology is best described as follows: spills have, until recendy (2), relied on mor- effects of pollutants on gene pools of fish "To assess, predict, and prevent signifi- tality censuses of exposed animals and have (10) and natural microbial communities cant radiation- or chemical-induced genetic not often considered sublethal genotoxicity. (11). New molecular capabilities should and epigenetic damage in populations." Although ozone depletion has received heighten the impact ofsuch research. Practically, attaining this goal will be enormous international attention, only a We now recognize that pervasive global demanding, in part because "significant few studies have examined the damaging pollution requires that the effects of haz- genetic damage" is difficult to define and effects of increased UV-B on DNA of wild ardous substances on biodiversity be well- therefore difficult to measure, and because organisms, even in the affected Antarctic studied. Several lines of evidence have our ability to predict the consequences of ecosystem (3). In agricultural settings shown that pollutants cause decreased such change is inadequate. throughout the world, genotoxic com- genetic variability in populations and that There are at least two possible definitions pounds are used as pesticides and herbicides, such decreases are detrimental to popula- of "significant genetic damage." The first yet we know that some of these substances tion viability (10,12). Others (13-16) definition is based on a population-level can elicit adverse genetic and epigenetic have raised the concern that pollutants focus: responses in nontarget populations (4). could affect evolutionary processes. Thus, Definition 1. Significant genetic dam- Additionally, global mining practices have it is vital that we consider research in age is defined as altered genetic structure or mobilized tons ofhazardous mutagenic met- genetic ecotoxicology as crucial to conserv- function in individuals that ultimately als such as arsenic, mercury, nickel, and ing the genetic variability contained within results in decreased