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N-nitroso compounds induce changes in carcinogen-metabolizing enzymes
1Department of Environmental Studies, Alexandria University, Egypt.
Cancer Letters
|September 10, 1996
Summary
N-nitroso compounds significantly alter liver enzyme activities. Some increase dimethylnitrosamine N-demethylase I (DMN-dI) and cytochrome P-450, while others decrease them, showing varied effects on mixed function oxidase system enzymes.
Area of Science:
- Biochemistry
- Toxicology
- Enzymology
Background:
- The bioactivation of N-nitrosoamines and polycyclic aromatic hydrocarbons (PAH) is crucial for their toxicological effects.
- This bioactivation is primarily mediated by the liver's mixed function oxidase (MFO) system, involving key enzymes like cytochrome P-450 and arylhydrocarbon hydroxylase (AHH).
- Understanding how specific compounds influence these enzymes is vital for assessing toxicological risks.
Purpose of the Study:
- To investigate the impact of various N-nitroso compounds on the activities of specific MFO system enzymes.
- To determine the relationship between N-nitroso compound structure and their effects on enzyme activity.
- To elucidate potential dependencies between different MFO enzymes, such as AHH and cytochrome P-450.
Main Methods:
- Male mice were administered a single dose (20 mg/kg body weight) of different N-nitroso compounds.
- Enzyme activities, including dimethylnitrosamine N-demethylase I (DMN-dI), arylhydrocarbon hydroxylase (AHH), and NADPH-cytochrome c reductase, were measured.
- Cytochrome P-450 and cytochrome b5 content were also quantified in liver microsomes.
Main Results:
- Ethylbutylnitrosamine, propylbutylnitrosamine, and dibutylnitrosamine increased DMN-dI, cytochrome P-450, AHH, and cytochrome b5 activities, while decreasing NADPH-cytochrome c reductase.
- Methylpropylnitrosamine and diphenylnitrosamine showed varied effects, with some decreasing DMN-dI and P-450, and diphenylnitrosamine decreasing AHH but increasing DMN-dI, cytochrome b5, and NADPH-cytochrome c reductase.
- AHH activity appeared to correlate with P-450 content, whereas DMN-dI activity did not show a consistent parallel.
Conclusions:
- The type of alkyl groups attached to the nitroso group significantly influences the extent of alteration in MFO enzyme activities.
- The study suggests a potential co-regulation of AHH and P-450, but not necessarily DMN-dI.
- These findings highlight the complex interactions within the MFO system in response to N-nitroso compound exposure.