Concentration-dependent protection against X-ray-induced chromosome aberrations in human lymphocytes by the aminothiol WR-1065.
WR-1065, the free-thiol form of WR-2721, has radioprotective effects in various biological systems. We measured the efficiency of WR-1065 in modifying the induction of chromosome aberrations by X rays in human lymphocytes. G0 lymphocytes were incubated for 30 min in medium containing 1-12 mM WR-1065, exposed to 0 or 3.1 Gy 220-kV X rays, washed, and cultured for evaluations of chromosome aberrations and micronuclei (MN). Neither proliferation kinetics nor baseline frequencies of aberrations or MN were affected in nonirradiated cultures incubated in WR-1065 for up to 45 min. Radiation-induced chromosome aberrations and MN varied inversely as a logarithmic function of thiol concentration. At extracellular concentrations of 8-12 mM, WR-1065 protected against > 85% of X-ray-induced chromosome damage as measured by either cytogenetic end point. WR-1065 is more efficient in modulating X-ray-induced chromosome aberrations than dimethyl sulfoxide, which provides protection by scavenging OH radicals. Our data suggest that mechanisms in addition to OH radical scavenging are involved in radioprotection by WR-1065.
Littlefield
L G
LG
Oak Ridge Institute of Science and Education, Tennessee 37831-0117.
Joiner
E E
EE
Colyer
S P
SP
Sallam
F
F
Frome
E L
EL
D002869:Chromosome Aberrations; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D008624:Mercaptoethylamines / Q000627:therapeutic use*; D048629:Micronuclei, Chromosome-Defective; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane