Abstract

The long-term goal of the proposed research is to investigate alkene metabolism. The extent of alkene oxidation and the role of aliphatic epoxide (alkene oxides) as intermediates in such biotransformations are to be studied. An initial aim is to extend our structure-mutagenicty relationships for alkene oxides and compare them to glutathione and hydratase detoxification systems. DNA binding studies and characterization of the site of binding will be conducted for selected epoxides. Such binding studies are of particular interest for those epoxides showing a high ratio of mutagenicity to detoxification as a further indication of their toxicity and carcinogenicity. The proposed studies of alkene oxides as related to alkene metabolism would be analogous to the more established role of arene oxides in the toxicity and detoxification of aromatic compounds.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003345-06
Application #
3250565
Study Section
Toxicology Study Section (TOX)
Project Start
1983-09-28
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Pharmacy
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Sinsheimer, J E; Chen, R; Das, S K et al. (1993) The genotoxicity of enantiomeric aliphatic epoxides. Mutat Res 298:197-206
Tan, R S; Chu, E H; Sinsheimer, J E (1993) Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1-naphthyl ether in mouse spleen cells in vivo. Environ Mol Mutagen 22:71-7
Einisto, P; Hooberman, B H; Sinsheimer, J E (1993) Base-pair mutations caused by six aliphatic epoxides in Salmonella typhimurium TA100, TA104, TA4001, and TA4006. Environ Mol Mutagen 21:253-7
Hooberman, B H; Chakraborty, P K; Sinsheimer, J E (1993) Quantitative structure-activity relationships for the mutagenicity of propylene oxides with Salmonella. Mutat Res 299:85-93
Das, L; Das, S K; Chu, E H et al. (1993) Chromosomal aberrations in mouse lymphocytes exposed in vivo and in vitro to aliphatic epoxides. Mutat Res 299:19-24
Chen, R; Nguyen, P; You, Z et al. (1993) Enantioselective detoxication of optical isomers of glycidyl ethers. Chirality 5:501-4
Sinsheimer, J E; Hooberman, B H; Das, S K et al. (1992) Genotoxicity of chryseno[4,5-bcd]thiophene and its sulfone derivative. Environ Mol Mutagen 19:259-64
van den Eeckhout, E; Coene, J; Claereboudt, J et al. (1991) Comparison of the isolation of adducts of 2'-deoxycytidine and 2'-deoxyguanosine with phenylglycidyl ether by high-performance liquid chromatography on a reversed-phase column and a polystyrene-divinylbenzene column. J Chromatogr 541:317-31
Sinsheimer, J E; Giri, A K; Hooberman, B H et al. (1991) Mutagenicity in Salmonella and sister chromatid exchange in mice for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrenes. Environ Mol Mutagen 17:93-7
Giri, A K; Messerly, E A; Chakraborty, P K et al. (1990) DNA strand breaks in liver for four aliphatic epoxides in mice. Mutat Res 242:187-94

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