Abstract

The general aim of this proposal continues to be the study of the relationship between benzene metabolism and benzene toxicity. In this grant period we wish to investigate the covalent binding of benzene to DNA using isolated enzyme and cell systems to produce biological reactive intermediates of benzene and added DNA. We will then compare the adducts formed in these systems with those formed by the administration of benzene in vivo. The adducts formed in vivo will be measured using the """"""""post labeling assay"""""""". We also plan to study the effects of benzene on the production of cell growth factors. Thus, we will determine the effects of benzene and its metabolites on the ability of the T-lymphocyte to produce the hematopoietic factors IL-3(multiCSA) and granulocyte/macrophage colony stimulating activity (GM-CSA). We will also determine the effects of benzene on the monocyte-directed production and/or release of hematopoietic factors by the T-lymphocyte.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002931-07
Application #
3250168
Study Section
Safety and Occupational Health Study Section (SOH)
Project Start
1981-09-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Type
Schools of Pharmacy
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901

  Publications

Snyder, R; Chepiga, T; Yang, C S et al. (1993) Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5, microsomal epoxide hydrolase, and glutathione transferases: evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquino Toxicol Appl Pharmacol 122:172-81
Guy, R L; Dimitriadis, E A; Hu, P D et al. (1990) Interactive inhibition of erythroid 59Fe utilization by benzene metabolites in female mice. Chem Biol Interact 74:55-62
Jowa, L; Witz, G; Snyder, R et al. (1990) Synthesis and characterization of deoxyguanosine-benzoquinone adducts. J Appl Toxicol 10:47-54
Laskin, D L; MacEachern, L; Snyder, R (1989) Activation of bone marrow phagocytes following benzene treatment of mice. Environ Health Perspect 82:75-9
Bauer, H; Dimitriadis, E A; Snyder, R (1989) An in vivo study of benzene metabolite DNA adduct formation in liver of male New Zealand rabbits. Arch Toxicol 63:209-13
Snyder, R; Dimitriadis, E; Guy, R et al. (1989) Studies on the mechanism of benzene toxicity. Environ Health Perspect 82:31-5
Kalf, G F (1987) Recent advances in the metabolism and toxicity of benzene. Crit Rev Toxicol 18:141-59
Kalf, G F; Post, G B; Snyder, R (1987) Solvent toxicology: recent advances in the toxicology of benzene, the glycol ethers, and carbon tetrachloride. Annu Rev Pharmacol Toxicol 27:399-427
Snyder, R; Jowa, L; Witz, G et al. (1987) Formation of reactive metabolites from benzene. Arch Toxicol 60:61-4
Post, G; Snyder, R; Kalf, G F (1986) Metabolism of benzene and phenol in macrophages in vitro and the inhibition of RNA synthesis by benzene metabolites. Cell Biol Toxicol 2:231-46

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