1,3 Butadiene: Cancer, Mutations, and Adducts

Research Report 92,

Part I: Carcinogenicity of 1,2,3,4-Diepoxybutane Rogene F Henderson, Edward B Barr, Steven A Belinsky, Janet M Benson, Fletcher F Hahn, and Margaret Ménache

Part II: Roles of Two Metabolites of 1,3-Butadiene in Mediating Its in Vivo Genotoxicity Leslie Recio, Christopher J Saranko, and Ann-Marie Steen

Part III: In Vivo Mutation of the Endogenous hprt Genes of Mice and Rats by 1,3-Butadiene and Its Metabolites Vernon E Walker and Quanxin Meng

Part IV: Molecular Dosimetry of 1,3-Butadiene Ian A Blair, Tomoyki Oe, Sara Kambouris, and Ajai K Chaudhary

Part V: Hemoglobin Adducts as Biomarkers of 1,3-Butadiene Exposure and Metabolism James A Swenberg, Nadia I Christova-Gueorguieva, Patricia B Upton, Asoka Ranasinghe, Nova Scheller, Kuen-Yuk Wu, Ten-Yang Yen, and Richard Hayes

As part of the Health Effects Institute's air toxics research program, five independent studies were designed to advance our understanding of the roles of different metabolites in 1,3-butadiene (BD)-induced carcinogenesis and of the differences in sensitivity among species, and to develop methods for identifying and measuring biomarkers. The investigators focused on two BD metabolites (1,2-epoxy-3-butene [BDO] and 1,2,3,4-diepoxybutane [BDO2]) that researchers had suspected may play a role in BD carcinogenesis. Dr. Rogene Henderson (Lovelace Respiratory Research Institute) exposed mice and rats to BDO2 to determine whether these species differ in their carcinogenic response to this metabolite. Dr. Leslie Recio (CIIT) and Dr. Vernon Walker (New York State Department of Health) compared the mutagenicity of BD, BDO, and BDO2 in mice and rats. Dr. Ian Blair (University of Pennsylvania) developed methods for measuring DNA adducts derived from BD metabolites in the tissues and urine of rats and mice with the goal of comparing the levels of adducts in the two species and identifying possible biomarkers. Dr. James Swenberg (University of North Carolina at Chapel Hill) developed a sensitive method for detecting adducts formed between BD metabolites and a blood protein (hemoglobin) and measured these adducts in animals and humans exposed to BD.