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Decrease in the activity of hepatic microsomal drug-metabolizing enzymes in tumor-bearing nude mice
Abstract:
The activities of hepatic microsomal drug-metabolizing enzymes in nude mice (BALB/c-nu/nu) bearing tumors of human or nude mouse origin were studied. The content of cytochrome P-450 and the activities of cyclophosphamide oxidase, benzo[a]pyrene hydroxylase, aniline hydroxylase and benzphetamine N-demethylase were markedly decreased in tumor-bearing nude mice in accordance with previous observations in tumor-bearing rats and mice. These results indicate that decreases in the activities of hepatic microsomal drug-metabolizing enzymes are not the consequence of an immunoreactive process or cachexia.
Insights
Drug-metabolizing enzyme activity in nude mice with tumors significantly decreased. This reduction is independent of immune response or cachexia, suggesting a direct tumor-related effect on liver enzymes.
Area of Science:
- Pharmacology
- Biochemistry
- Cancer Biology
Background:
- Hepatic microsomal drug-metabolizing enzymes are crucial for xenobiotic and endogenous compound processing.
- Tumor-bearing hosts often exhibit altered drug metabolism, impacting treatment efficacy.
- Nude mice (BALB/c-nu/nu) are valuable models for studying human tumors due to their immunodeficiency.
Purpose of the Study:
- To investigate the impact of tumors on hepatic microsomal drug-metabolizing enzyme activities in nude mice.
- To determine if observed enzyme activity changes are linked to immunoreactivity or cachexia.
Main Methods:
- Assessed cytochrome P-450 content in tumor-bearing nude mice.
- Measured activities of key drug-metabolizing enzymes: cyclophosphamide oxidase, benzo[a]pyrene hydroxylase, aniline hydroxylase, and benzphetamine N-demethylase.
- Compared enzyme levels and activities in tumor-bearing mice with control groups (implied).
Main Results:
- Marked decreases in cytochrome P-450 content were observed.
- Significant reductions in the activities of cyclophosphamide oxidase, benzo[a]pyrene hydroxylase, aniline hydroxylase, and benzphetamine N-demethylase were noted.
- These enzyme alterations occurred in nude mice bearing tumors of both human and nude mouse origin.
Conclusions:
- Tumor burden in nude mice leads to a significant decrease in hepatic microsomal drug-metabolizing enzyme activities.
- The observed reductions are not attributable to the host's immune response or cachexia.
- These findings suggest a direct influence of the tumor on the metabolic capacity of the liver.