Conformational changes in chromatin structure induced by the radioprotective aminothiol, WR 1065.
WR 1065, 2-[(minopropyl) amino] ethanethiol is an effective scavenger of free radicals. When present during irradiation it reduces cellular DNA damage as analysed by alkaline elution from filters. The same technique indicates that without irradiation, WR 1065 has no effect of DNA integrity. Using nucleoid analysis, where DNA damage is detected at the level of replicon clusters, WR 1065 distorts replicon supercoiling without breaking the DNA molecule. This confirmational change in nucleoid structure occurs with no detectable change in nucleoid protein content. It is proposed that perturbation of replicon supercoiling affects the process of normal DNA synthesis and strand break rejoining, allowing a longer time for the accurate repair of DNA damage.
Vaughan
A T
AT
Division of Biological and Medical Research, Argonne National Laboratory, IL 60349.
Grdina
D J
DJ
Meechan
P J
PJ
Milner
A E
AE
Gordon
D J
DJ
D000818:Animals; D002843:Chromatin; D006224:Cricetinae; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000528:radiation effects; D004278:DNA, Superhelical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D008624:Mercaptoethylamines / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D002843:Chromatin; D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane