Dose-rate effects for apoptosis and micronucleus formation in gamma-irradiated human lymphocytes.
We have compared dose-rate effects for gamma-radiation-induced apoptosis and micronucleus formation in human lymphocytes. Long-term assessment of individual radiation-induced apoptosis showed little intraindividual variation but significant interindividual variation. The effectiveness of radiation exposure to cause apoptosis or micronucleus formation was reduced by low-dose-rate exposures, but the reduction was apparent at different dose rates for these two end points. Micronucleus formation showed a dose-rate effect when the dose rate was lowered to 0.29 cGy/min, but there was no accompanying cell cycle delay. A further increase in the dose-rate effect was seen at 0.15 cGy/min, but was now accompanied by cell cycle delay. There was no dose-rate effect for the induction of apoptosis until the dose rate was reduced to 0.15 cGy/min, indicating that the mechanisms or signals for processing radiation-induced lesions for these two end points must be different at least in part. There appear to be two mechanisms that contribute to the dose-rate effect for micronucleus formation. One of these does not affect binucleate cell frequency and occurs at dose rates higher than that required to produce a dose-rate effect for apoptosis, and one affects binucleate cell frequency, induced only at the very low dose rate which coincidentally produces a dose-rate effect for apoptosis. Since the dose rate at which cells showed reduced apoptosis as well as a further reduction in micronucleus formation was very low, we conclude that the processing of the radiation-induced lesions that induce apoptosis, and some micronuclei, is very slow in quiescent and PHA-stimulated lymphocytes, respectively.
Boreham
D R
DR
AECL, Chalk River Laboratories, Chalk River, Ontario, Canada, K0J 1J0.
Dolling
J A
JA
Maves
S R
SR
Siwarungsun
N
N
Mitchel
R E
RE
D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective