PH Regulation by Breast Cancer Cells In Vitro and In Vivo.
Abstract
The pH of tumors plays an important role in the efficacy of chemotherapy and radiotherapy and may have relevance to carcmogenesis itself. During the past year, we have generated a quantitative model and empirical evidence to support a role for the recycling of endocytic vesicles in the resistance to weakly basic chemotherapeutic drugs (Project 1). A spinoff of this project is the isolation of these acidic vesicles and characterization of their activity. A technique has been developed to simultaneously measure the extracellular and intracellular p11 of tumors using magnetic resonance spectroscopy (MRS, project 2). This technique has been refined to accurately report the entire extracellular pH range within an entire tumor. This is significant because acidic pH is both clastogenic and mutagenic. As a result of these measurements we have been able to design and monitor protocols to chronically raise the extracellular pH of tumors (Project 3). The effect of these treatments on chemosensitivity is being tested. Finally, because extracellular pH in tumors is expected to be heterogenous, we have begun developing methods to measure pHe using 1-H MRS of exogenous imidazoles (project 4). With this method, we will be able to generate maps of pHe in living tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA337859
Entities
People
- Robert J Gillies
Organizations
- University of Arizona