Evaluation of the Use of DNA Adduct Dosimetry to Optimize the Timing of High Dose Therapy for Breast Cancer
Abstract
For drugs that interact with DNA, measures of DNA damage can assess the intracellular availability of active drug at a critical molecular target. Measurements of DNA damage should reflect the integrated effect of all resistance factors, including both recognized mechanisms and uncharacterized mechanisms. Thus, molecular measures of DNA damage could provide an important tool for elucidating the time course of complex changes in resistance factors. Motivated by a recent clinical trial that demonstrated better survival when the interval between induction chemotherapy and high dose therapy was prolonged, this project is using measures of DNA damage in patient blood cells to determine whether induction chemotherapy causes transient changes in resistance. Findings indicate cyclophosphamide, cis-platin, and BCNU each produce DNA damage that can be measured in a dose dependent manner. At low doses each agent causes a similar pattern of breakage, while at high doses their pattern of damage could be distinguished. Both lymphocytes and bone marrow cells from patients can be routinely analyzed, allowing study of changes in sensitivity in multiple tissues. It is feasible to use the procedure to study whether induction therapy has a transient effect on resistance to high dose therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA401099
Entities
People
- Richard B. Everson
Organizations
- Wayne State University