- Collection:
- Atlanta University and Clark Atlanta University Theses and Dissertations
- Title:
- The effects of two factors on the induction of cytochrome p450 system: aging and treatment with polycyclic aromatic hydrocarbons, 1981
- Creator:
- Demons, Samuel H.
- Date of Original:
- 1981-07-01
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- theses
- Type:
- Text
- Format:
- application/pdf
- Description:
- The purpose of this research project was to investigate the effect of aging and treatment with polycyclic aromatic hydrocarbons on an hepatic microsomal system, the cytochrome P450. An examination was made on the ability of this system, following treatment with test chemicals (20, 40, 60 days test period), to activate 2-aminofluorene. The Salmonella typhimurium histidine revertant assay, which is specific for detecting certain frameshift and base substitutions, was employed. The liver microsomal activation system was incorporated directly into the top agar with the bacterial strain and the test sample. This system was used to analyze the mutagenic character of low dosage test sample in concentrations found in finished drinking water (12 ug/1) and the effect of aging on the liver microsomal activation potential. Following mutagenic assays, the specific activity of liver enzyme (cytochrome P450) from each sample was determined, and a definite correlation between specific activity of liver enzyme and mutagenic activity was discovered. As mutagenic activity increases so does specific activity of the liver enzyme. Gel electrophoresis of 60 days induced tissues, because of their higher mutagenic response, was selected for analysis. Multiple forms of cytochrome P450 showed indications of being produced by one chemical. The phenomenon of increased synthesis of one form of cytochrome P450 occurring at the expense of another seemed to be operative. The effect of aging on liver microsomal activation produced clear trends relating to cytochrome P450. Although induced and uninduced animals showed increased activity as a function of age such activity was not maintained throughout with uninduced animals. However, old rats respond to exogenous inducers as well as or better than young animals, indicating no true impairment in regulation of hepatic drug metabolism.
- External Identifiers:
- Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.td:1981_demons_samuel_h
- Rights Holder:
- Clark Atlanta University
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights:
-
