Effect of Folate on the Efficacy and Toxicity of Cancer Chemotherapy
Abstract
The purpose of this research project was to characterize the effect of dietary folate levels on the cellular pharmacology and toxicology of chemotherapeutic agents. The scope of the research involved in vitro studies with cell lines and in vivo assessments in rats of folate-chemotherapy interactions. Studies at a molecular level with human cells confirmed the model developed in rodent cells to explain the synergy between nutritional folate deficiency and alkylating agents. Cells expressing p53 activity exhibited a higher rate of mutation induction but were more sensitive to the toxic effects of alkylating agents than those lacking p53. Folate deficiency tended to reduce toxicity but increase mutation induction after alkylator treatment. Studies in rat liver confirmed that folate metabolism modulates glutathione levels. Studies in rats of the interaction of diet and cyclophosphamide indicated that deaths were predicted by dose and diet. The combination of high doses of folate and chemotherapy caused renal damage, indicating that there may be an optimal amount of dietary folate to modulate toxicity. Folate supplementation decreased the frequency of mitochondrial DNA deletions in liver from untreated rats and from animals treated with cyclophosphamide. Studies with 5-fluorouracil confirmed that dietary changes profoundly affect the outcome of cancer chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2001
- Accession Number
- ADA405558
Entities
People
- Richard F. Branda
Organizations
- University of Vermont