Abstract

The objectives of the proposed research concerning activation and detoxification of toxic and carcinogenic haloalkenes are enumerated below: 1) Determination of the alkylating agents involved in the covalent binding of vinyl chloride, vinylidene chloride, trichloroethylene, vinyl bromide and acrylonitrile to protein and nucleic acids, 2) elucidation of the role of epoxide hydratase in the metabolism of vinyl halides in vivo and in vitro, 3) immunohistochemical localization of epoxide hydratase in liver and lung, 4) examination of vinyl halide metablism in the lung in vitro, 5) determination of the mechanism of cytochrome P-450 heme destruction that occurs during haloalkene metabolism, and 6) examination of DNA-chromatin protein crosslinking by metabolites of haloalkenes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002205-07
Application #
3249684
Study Section
Toxicology Study Section (TOX)
Project Start
1979-06-25
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Guengerich, F Peter (2004) Cytochrome P450: what have we learned and what are the future issues? Drug Metab Rev 36:159-97
Guengerich, F P; Kim, D H; Iwasaki, M (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168-79
Guengerich, F P; Kim, D H (1991) Enzymatic oxidation of ethyl carbamate to vinyl carbamate and its role as an intermediate in the formation of 1,N6-ethenoadenosine. Chem Res Toxicol 4:413-21
Guengerich, F P (1988) Cytochromes P-450. Comp Biochem Physiol C 89:1-4
Veltman, J C; Dekant, W; Guengerich, F P et al. (1988) Cytotoxicity and bioactivation mechanism of benzyl 2-chloro-1,1,2-trifluoroethyl sulfide and benzyl 1,2,3,4,4-pentachlorobuta-1,3-dienyl sulfide. Chem Res Toxicol 1:35-40
Baron, J; Burke, J P; Guengerich, F P et al. (1988) Sites for xenobiotic activation and detoxication within the respiratory tract: implications for chemically induced toxicity. Toxicol Appl Pharmacol 93:493-505
Guengerich, F P (1988) Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res 48:2946-54
Schaefer, W H; Harris, T M; Guengerich, F P (1987) Reaction of the model thiol 2-mercaptoethanol and glutathione with methylvinylmaleimide, a Michael acceptor with extended conjugation. Arch Biochem Biophys 257:186-93
Guengerich, F P (1986) Covalent binding to apoprotein is a major fate of heme in a variety of reactions in which cytochrome P-450 is destroyed. Biochem Biophys Res Commun 138:193-8
Hogy, L L; Guengerich, F P (1986) In vivo interaction of acrylonitrile and 2-cyanoethylene oxide with DNA in rats. Cancer Res 46:3932-8

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