Hprt mutations in human T-lymphocytes reflect radioprotective effects of the aminothiol, WR-1065.
Aminothiols such as WR-2721 and its active free thiol WR-1065 have previously been shown to reduce mutations resulting from ionizing radiation in exponentially growing cells. In this study, non-dividing human G0 T-lymphocytes were exposed to the aminothiol radioprotective agent, WR-1065, 30 min before or 3 h after external beam gamma-irradiation and subsequently assessed for survival and mutation induction at the hprt locus. Cytotoxicity due to gamma-irradiation was reduced only when the WR-1065 was present during irradiation. The frequency of hprt mutations, however, was reduced regardless of time of administration, although the reduction was statistically significant only when WR-1065 was added 30 min before irradiation (P < 0.01). This is the first study to demonstrate the protective effects of WR-1065 against radiation-induced mutation in a reporter gene using a human non-cycling cell. Hprt mutations arising in vivo in these cells may be useful for monitoring the radioprotective effect of aminothiols in human populations.
Clark
L S
LS
Vermont Cancer Center Genetics Laboratory, University of Vermont, Burlington 05401, USA.
Albertini
R J
RJ
Nicklas
J A
JA
D016587:Antimutagenic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000528:radiation effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008624:Mercaptoethylamines / Q000494:pharmacology*; D009154:Mutation; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000528:radiation effects*
D016587:Antimutagenic Agents; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D007041:Hypoxanthine Phosphoribosyltransferase