Polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants that possess toxic, mutagenic and carcinogenic properties. A considerable amount of research effort has been directed towards studies on the mammalian oxidation of this class of compounds. However, almost nothing is known about their interaction with microorganisms. The major objective of this research proposal is to elucidate the mechanisms used by bacteria and fungi to oxidize benzo[a]pyrene, benzo[a]anthracene and 3-methylcholanthrene. Such studies will involve the disciplines of chemistry, biochemistry and enzymology and should provide information relative to the fate of these compounds in the environment and the development of methods for their removal. In addition, basis information relevant to studies on the metabolism of carcinogenic hydrocarbons by higher organisms will also be obtained. Studies on the degradation of benzo[a]pyrene, benzo[a]anthracene and 3-methylcholanthrene by bacteria will involve the isolation of mutant strains that accumulate degradation products. Each metabolite will be isolated and identified by modern chemical techniques. The unique enzyme(s) responsible for initiating the oxidation of carcinogenic hydrocarbons will be purified and their mechanism of action elucidates. Cytochrome P-450 and epoxide hydrolase will be purified from cells of the filamentous fungus, Cunninghamella elegans. The purified enzymes will be used to probe the anatiomeric specificity involved in the formation of carcinogenic metabolites from benzo[a]pyrene.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA019078-11
Application #
3165085
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1979-07-01
Project End
1988-04-30
Budget Start
1986-05-01
Budget End
1988-04-30
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713
Narro, M L; Cerniglia, C E; Van Baalen, C et al. (1992) Evidence for an NIH shift in oxidation of naphthalene by the marine cyanobacterium Oscillatoria sp. strain JCM. Appl Environ Microbiol 58:1360-3
Mahaffey, W R; Gibson, D T; Cerniglia, C E (1988) Bacterial oxidation of chemical carcinogens: formation of polycyclic aromatic acids from benz[a]anthracene. Appl Environ Microbiol 54:2415-23