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Pathological features of glutaminase toxicity
British Journal of Experimental Pathology
|April 1, 1980
Summary
Chemically modified glutaminase caused severe toxicity in animal models, leading to fatal illness, diarrhea, and colitis. Even low doses induced adverse effects, highlighting significant safety concerns for this anti-tumor enzyme.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Glutaminase is an anti-tumor enzyme.
- Investigating the toxicity of modified glutaminase is crucial for its therapeutic development.
Purpose of the Study:
- To assess the toxicity of chemically modified glutaminase in various animal models.
- To identify pathological lesions associated with glutaminase administration.
Main Methods:
- Parenteral administration of varying doses of chemically modified glutaminase.
- Observation of clinical signs and mortality in Rhesus monkeys, marmosets, rabbits, and mice.
- Pathological examination for tissue lesions.
Main Results:
- Glutaminase induced diarrhea and dysentery across all tested species.
- Illness and mortality within 10 days were observed at all but the lowest doses.
- Pathological findings included hepatic lipidosis, glycogen accumulation, and acute necrotizing colitis in primates.
Conclusions:
- Chemically modified glutaminase exhibits significant toxicity.
- The observed pathological lesions suggest a narrow therapeutic window for glutaminase-based therapies.
- Further research is needed to mitigate the adverse effects of glutaminase for potential anti-tumor applications.