Effects of WR-1065 and WR-151326 on survival and neoplastic transformation in C3H/10T1/2 cells exposed to TRIGA or JANUS fission neutrons.
We demonstrated the ability of aminothiols WR-1065 and WR-151326, each at concentration 1 mM, to protect C3H/10T1/2 cells against the transforming effects of fission neutrons under two distinct sets of experimental conditions. Experiments with WR-1065 were performed with stationary cultures of C3H/10T1/2 cells, and a TRIGA reactor-generated fission neutron field at the Armed Forces Radiobiology Research Institute (USA). Experiments with WR-151326 were performed with proliferating cultures of C3H/10T1/2 cells and a JANUS reactor-generated fission neutron field at the Argonne National Laboratory (USA). Radioprotectors were present before, during, and after irradiation for total-periods of 35 min (WR-151326; 10 min pre-incubation) or 1 h (WR-1065; 30 min pre-incubation). Bioavailability of WR-1065 and WR-151326 in extracellular medium under experimental conditions simulating those of the transformation experiments was studied by measuring oxidation rates in the presence of attached C3H/10T1/2 cells in plateau and exponential phase of growth for periods of up to 5 h. Estimated half-lives for autoxidation of WR-1065 or WR-151326 were approximately 8 min or 1 h regardless of the proliferative status of cells. In the absence of WR-compounds, dose-response data for transformation induction by neutrons from TRIGA and JANUS reactors were fitted to a common curve with a linear coefficient of about 7 x 10(-4)/Gy. WR-151326 and WR-1065 were found to provide significant radioprotection by factors of 1.79 +/- 0.08 and 3.23 +/- 0.19, respectively, against fission neutron-induced neoplastic transformation. No significant protection against neutron-induced cell lethality was observed.
Balcer-Kubiczek
E K
EK
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore 21201.
Harrison
G H
GH
Hill
C K
CK
Blakely
W F
WF
D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D066298:In Vitro Techniques; D008624:Mercaptoethylamines / Q000494:pharmacology*; D051379:Mice; D009502:Neutrons; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; C058704:3-(3-methylaminopropylamino)propylmercaptan