Subject(s)
Cell Proliferation/drug effects , Radiation-Protective Agents/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Cell Proliferation/radiation effects , Cells, Cultured , Cricetinae , Cricetulus , Diamide/pharmacology , Dimethyl Sulfoxide/pharmacology , History, 20th CenturyABSTRACT
Populations of G1-phase Chinese hamster cells in stirred suspensions containing various concentrations of DMSO were irradiated with 250 kV X-rays or various heavy charged-particle beams. Chemical radioprotection of cell inactivation was observed for all LET values studied. When cell survival data were resolved into linear and quadratic components, the extent and concentration dependence of DMSO protection were found to be different for the two mechanisms. The chemical kinetics of radioprotection for single-events were similar for LET values up to those which gave the maximum RBE. DMSO protected to a lesser extent against energetic argon ions at an median LET of approximately 220 keV/micron. These data could indicate the contribution of indirect action by hydroxyl radicals and hydrogen atoms to cell inactivation by single-hit and double-hit mechanisms for various radiation qualities. The decrease in RBE observed at very high LET may result, in part, from reduced yields of water radicals at 10(-9)-10(-8) s resulting from radical recombination mechanisms within the charged particle tracks.
Subject(s)
Dimethyl Sulfoxide/therapeutic use , Radiation-Protective Agents , Animals , Argon , Carbon , Cell Survival/radiation effects , Cricetinae , Energy Transfer , Helium , Ions , Mitosis/radiation effects , Neon , Particle Accelerators , X-RaysABSTRACT
Nitropyrrole derivatives have been tested as hypoxic cell radiosensitizers in vitro and in vivo. Radiosensitizing potential generally increases with nitropyrrole electron affinity. N-hydroxyethyl substitution decreases toxicity relative to N--CH3, N--CH2 CH3 and N--CH2 CH2 CH3 substitution. The most effective nitropyrrole tested in vivo is N-hydroxyethyl-2-cyano-5-nitropyrrole (NP-1).
Subject(s)
Pyrroles/pharmacology , Radiation-Sensitizing Agents , Animals , Cell Survival/drug effects , Cell Survival/radiation effects , In Vitro Techniques , Mice , Neoplasms, Experimental/radiotherapy , Oxygen Consumption/drug effects , Structure-Activity RelationshipABSTRACT
The chain of reactions, resulting in mutation and cell death, initiated when ionizing radiation interacts with mammalian cells is complex and traverses a time-scale from a fraction of a picosecond to a few hours. Recently, progress has been made in identifying some of the more important pathways and potentially damaging free radical intermediates. Protection can, in principle, result from modification at several steps in these reaction chains, each with its distinctive time-scale. To date we have demonstrated that radio-protection can be effected in mammalian cells by the modification of processes at three quite different times. In this paper, the temporal sequence of radiation-initiated events are reviewed and the potential for or measurement of radioprotection of each is discussed. Such an understanding of cellualr radioprotection has become possible by our improved understanding of cellular radiation mechanisms derived from recent studies of its chemistry [1-4].
