Biological Evaluation of Radioprotective Drugs
Abstract
The cellular and molecular mechanisms of radioprotection by aminothiols have been investigated through the use of cultured mammalian (CHO) cells and a whole-animal model, specific-pathogen free mice. For each of these systems, detailed structure-activity relationships were determined relating the effects of the different drugs on various endpoints for the survival of clonogenic cells and on the induction and repair of several types of DNA lesions in these same cells. The data with cultured cells have been used as a means of understanding or predicting the effects of the phosphate-blocked derivatives of these thiols on tissues. The major finding from the in vitro studies is the fact that the modulation of cell survival and DNA double-strand break induction correlates closely for a series of structurally-different thiols and aminothiols. The in vivo studies suggest that tissue oxygenation plays an important role in determining both the extent and mechanism of protection, and that understanding the interrelationships between oxygen, aminothiols and radiation sensitivity will be a crucial step in our ability to utilize such drugs effectively. Keywords: RA V; Radiation protection; Drugs; Drug screen; Mice; DNA damage; Animal survival; Cell survival; Bone marrow; Jejunun; Cultured cells; Aminothiols; Radioprotection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1988
- Accession Number
- ADA205818
Entities
People
- David Murray
Organizations
- The University of Texas MD Anderson Cancer Center