Thesis
In vitro metabolism of benzo(a)pyrene-7,8-dihydrol and dibenzo(def, p)chrysene-11,12 diol in rodent and human hepatic microsomes
Washington State University
Master of Science (MS), Washington State University
12/2015
Handle:
https://hdl.handle.net/2376/101329
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are contaminates ubiquitously found in the environment which are often carcinogenic and produced through anthropogenic combustion of organic matter. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P-diol), dibenzo[def,p]chrysene11,12 diol (DBC Diol), which are highly reactive metabolites that readily reactive with DNA. Metabolism of B[a]P-diol and DBC-Diol was studied in hepatic microsomes of female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Michaelis-Menten kinetic parameters including affinity constants (KM, µM), maximum rates of metabolism (VMAX, nmol/min/mg microsomal protein), and rates of intrinsic clearance (CLINT, ml/min/kg body weight) were calculated from substrate depletion data. CLINT rates were also determined using a linear regression method. Clearances rates of B[a]P-Diol were highest in the mouse and lowest for the human. Clearance rates of DBC-Diol were non-saturable for the mouse and human, but saturable for the rat. For both B[a]P-diol and DBC-diol the mouse had the highest clearance rates. Generally diol metabolite clearance is much greater than the parent compound clearance previously studied.
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Details
- Title
- In vitro metabolism of benzo(a)pyrene-7,8-dihydrol and dibenzo(def, p)chrysene-11,12 diol in rodent and human hepatic microsomes
- Creators
- Denis Mehinagic
- Contributors
- Yonas K. Demissie (Chair)Richard Corley (Committee Member)Mohiuddin Khan (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Civil and Environmental Engineering, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Number of pages
- 32
- Identifiers
- 99900525082801842
- Language
- English
- Resource Type
- Thesis