The proposed research program involves researchers and administrative staff from five institutions: the University of California at Berkeley, University of California at San Francisco, Californi Department of Health Services, Lawrence Berkeley Laboratory and Lawrence Livermore National Laboratory. A total of twelve projects are proposed which will be supported by five cores. These projects cover a wide range of Superfund related areas and chemicals, and address the relationship between hazardous substances in the environment and their impact on human health and ecosystem viability. The research proposed has five specific goals: 1. To develop and apply biomarkers in studies of human carcinogenesis; 2. To use biomarkers to determine the causes of genetic and reproductive damage in humans and ecosystems; 3. To better understand gender and ethnic differences in susceptibility to the toxic effects of Superfund chemicals; 4. To better understand the release and transport of toxic metals and other contaminants from inactive mining sites and from various combustion processes; 5. To improve methods of remediation at sites contaminated by volatile solvents and toxic metals. Project 1 -3 will aim to develop novel biomarkers of exposure and dose to specific targets in the human body. By identifying the specific molecular targets which Superfund chemicals attack in the body it would be possible to design much better biomarkers of delivered dose to target. Project 4, on biomarkers of susceptibility, will explore the role of polymorphisms in glutathione transferases with regard to susceptibility to childhood leukemia and arsenic-induced bladder cancer. Project 5 aims to develop highly predictive biomarkers of leukemia risk with the aim of understanding the causes of leukemia in humans. Project 6 will study environmental chemical exposure of parents and children and its relationship to the development of childhood leukemia. Project 7 will continue to study the role of arsenic in producing internal cancers in humans. A new Project 8 will study the role of male-mediated genotoxicity in lowered reproductive health. Project 9 will study the multigenerational effects of environmental mutagens on ecosystem viability. Project 10 will study the transport and fate of toxic metals including arsenic at inactive mining sites. Project 11 will continue to develop new methods for site remediation using steam injection and biodegradation. Project 12 will focus on understanding the factors which influence the production of toxic intermediates during combustion processes. Together these projects should address major issues of concern at Superfund sites through basic research, and thereby improve our ability to remediate hazardous waste sites and prevent the health effects posed by them. These projects will be supported by five cores, one of which focuses on children and the environment and aims to protect children from the toxic effects of environmental chemical exposures.