Contrasting Pathways for Activation of Two Cyclopentafused PAH in the Ames Assay: Identification of Metabolites of Benz[j]Aceanthrylene and Cyclopentafused Benzo[e]pyrene
Public Deposited- Last Modified
- February 28, 2019
- Creator
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Newcomb, Karyn O.
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- To determine the contribution of the diol-epoxide to the genotoxicity of benz[j]aceanthrylene (BjAA), the mutagenic activity of BjAA and its bay-region metabolites were evaluated in the Ames assay. BjAA, the 9,10-oxide, and the 9,lO-dihydrodiol are indirect acting mutagens with specific activities of 12.9 rev/nmole, 5.6 rev/nmol, and 9.4 rev/nmole, respectively. The 9,10-dihydrodiol-7,8-oxide was direct acting having the same activity as the parent compound, BjAA. Metabolism studies using Aroclor 1254 induced rat liver S9 were conducted on the BjAA-9,10-dihydrodiol metabolite. Four metabolites were isolated. Three metabolites were identified as 1,2,9,10-tetrahydro-l,2,9,10-tetrahydroxy-BjAA, 7,8,9,10-tetrahydro-7,8,9,10-tetrahydroxy-BJAA and the 9,10-dihydroxy-BjAA. The fourth metabolite was tentatively identified as BJAA-9,10-dihydrodiol-2-one. Similarly, the metabolism of cyclopentafused benzo[e]pyrene (cpBeP) was also investigated to determine whether the previously observed mutagenic activity of this compound was due to metabolism at the bay-region or the etheno bridge. Only one major metabolite was observed, the 3,4-dihydrodiol cpBeP. Additional minor metabolites were isolated, but not enough material was available to identify them. Oxidation occurs at the cyclopentafused ring for both BjAA and cpBeP when incubated with rat liver 59. This structure is of importance when considering mutagenic activation of a compound, and is an exception to the bay-region theory proposed by Jerina and colleagues.
- Date of publication
- January 1991
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Todd, Lori A.
- Gold, Avram
- Ball, Louise
- Degree
- Master of Science in Public Health
- Academic concentration
- Environmental Health Sciences
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 1991
- Language
- Deposit record
- ad7e9272-7c4f-43e0-afeb-7a5f2526ad76
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