1,3-Butadiene is a widely used chemical in the manufacture of synthetic rubber and other polymers. It is carcinogenic in laboratory animals and evidence of its carcinogenic effects in man have been greatly strengthened by a recent update of the ongoing evaluation of workers in the rubber industry which showed a significant association between butadiene exposure and leukemia. a more complete understanding of the health risks faced by workers exposed to levels of butadiene in facilities in use today is urgently needed. Furthermore, a large percentage of the general public is exposed daily to low levels of butadiene from auto emissions, cigarette smoke and other sources. We earlier documented that workers exposed to about 1 ppm of butadiene had a significant elevation in the frequency of mutations at the hprt gene in their lymphocytes. The purpose of this project is to evaluate current conditions of occupational exposure to butadiene using biological markers of exposure, effect and susceptibility. During the first cycle of this grant we confirmed our earlier finding of increased hprt mutant lymphocyte frequencies in workers. The research proposed for the renewal of this project will address three knowledge gaps: 1) better defining the relationship between butadiene exposure and biological effects, 2) characterizing the types of mutations induced by butadiene, and 3) the role of activating and detoxifying enzymes in the metabolism and genetic toxicity of butadiene. A previously studied population of workers in a styrene-butadiene polymer plant and a new population in a polybutadiene plant will be evaluated.
The specific aims of the project are 1) to more precisely define the relationship between exposure and hprt mutation induction using repeated measurements of air concentration of butadiene and the concentration of a urinary metabolite, 2) to determine the spectrum of hprt mutations in lymphocyte clones, and 3) to characterize the role of metabolism in individual susceptibility to the mutagenic effects of butadiene by determining polymorphic variations activating and detoxifying enzymes CYP 2E1 and GST T1 and M1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES006015-04
Application #
2701317
Study Section
Special Emphasis Panel (ZRG4-ALTX-2 (01))
Project Start
1993-08-01
Project End
2000-03-31
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Wickliffe, Jeffrey K; Ammenheuser, Marinel M; Adler, P Jene et al. (2009) Evaluation of frequencies of HPRT mutant lymphocytes in butadiene polymer workers in a Southeast Texas facility. Environ Mol Mutagen 50:82-7
Wickliffe, Jeffrey K; Herring, Stacy M; Hallberg, Lance M et al. (2007) Detoxification of olefinic epoxides and nucleotide excision repair of epoxide-mediated DNA damage: Insights from animal models examining human sensitivity to 1,3-butadiene. Chem Biol Interact 166:226-31
Wickliffe, J K; Galbert, L A; Ammenheuser, M M et al. (2006) 3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic mutations in Xpc-null mice. Environ Mol Mutagen 47:67-70
Abdel-Rahman, Sherif Z; Ammenheuser, Marinel M; Omiecinski, Curtis J et al. (2005) Variability in human sensitivity to 1,3-butadiene: influence of polymorphisms in the 5'-flanking region of the microsomal epoxide hydrolase gene (EPHX1). Toxicol Sci 85:624-31
Abdel-Rahman, Sherif Z; El-Zein, Randa A; Ammenheuser, Marinel M et al. (2003) Variability in human sensitivity to 1,3-butadiene: Influence of the allelic variants of the microsomal epoxide hydrolase gene. Environ Mol Mutagen 41:140-6
Ammenheuser, M M; Bechtold, W E; Abdel-Rahman, S Z et al. (2001) Assessment of 1,3-butadiene exposure in polymer production workers using HPRT mutations in lymphocytes as a biomarker. Environ Health Perspect 109:1249-55
Ward Jr, J B; Abdel-Rahman, S Z; Henderson, R F et al. (2001) Assessment of butadiene exposure in synthetic rubber manufacturing workers in Texas using frequencies of hprt mutant lymphocytes as a biomarker. Chem Biol Interact 135-136:465-83
Abdel-Rahman, S Z; Ammenheuser, M M; Ward Jr, J B (2001) Human sensitivity to 1,3-butadiene: role of microsomal epoxide hydrolase polymorphisms. Carcinogenesis 22:415-23
Ma, H; Wood, T G; Ammenheuser, M M et al. (2000) Molecular analysis of hprt mutant lymphocytes from 1, 3-butadiene-exposed workers. Environ Mol Mutagen 36:59-71
Ma, H; Smith, D H; Hsie, A W et al. (2000) Multiplex polymerase chain reaction-based analysis of T-cell receptor gamma gene rearrangements for the determination of T-lymphocyte clonality. Environ Mol Mutagen 35:8-Jan

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