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Characterization and induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in rabbit bone marrow
Abstract:
Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered.
Insights
Benzo(a)pyrene hydroxylase activity in rabbit bone marrow, particularly in white cells, suggests a role for mixed-function oxygenases in hemopoietic toxicity. This enzyme activity was NADPH dependent and CO sensitive.
Area of Science:
- Biochemistry
- Toxicology
- Hematology
Background:
- Bone marrow is a critical site for hematopoiesis.
- Mixed-function oxygenases (MFOs) metabolize xenobiotics.
- Cytochrome P-450 enzymes are key components of MFO systems.
Purpose of the Study:
- To investigate Benzo(a)pyrene (BP) hydroxylase activity in rabbit bone marrow.
- To characterize the properties and cellular localization of this activity.
- To explore the potential role of bone marrow MFOs in hemopoietic toxicity.
Main Methods:
- Enzyme assays were performed on bone marrow microsomes from control and 3-methylcholanthrene (3MC)-induced rabbits.
- NADPH and carbon monoxide (CO) dependence were assessed.
- Inhibition by 7,8-benzoflavone was evaluated.
- Cellular localization within bone marrow was determined.
Main Results:
- BP hydroxylase activity was detected in rabbit bone marrow microsomes.
- The activity was NADPH dependent and CO sensitive, characteristic of cytochrome P-450.
- 7,8-benzoflavone inhibited the activity, indicating involvement of the 3MC-inducible P-450 form.
- Activity was primarily located in white blood cells and was higher than in human lymphocytes/monocytes.
Conclusions:
- Rabbit bone marrow possesses significant BP hydroxylase activity, mediated by a 3MC-inducible cytochrome P-450.
- This activity is predominantly found in white cells.
- Bone marrow MFOs may play a role in causing hemopoietic toxicity.