INVERSE DOSE-RATE EFFECT FOR THE INDUCTION OF MICRONUCLEI IN LEWIS LUNG-CARCINOMA AFTER EXPOSURE TO CO-60 GAMMA-RAYS

Induction of micronuclei was used as a measure of the dose-rate effect in Lewis lung carcinoma in vivo. Tumors transplanted on the hind legs of male C57BL mice were irradiated at dose rates of 1 and 0.34 Gy/min , cells were isolated and cultured in vitro, and micronuclei were scor ed at 24-h intervals. Maximum expression of micronuclei was observed 7 2 h after plating. The frequency of cells containing micronuclei and t he number of micronuclei per single cell were linearly dependent on do se in the range 0-6 Gy. However, a marked inverse dependence on dose r ate was observed. The inverse dose-rate effectiveness factor, calculat ed as the ratio of damage per gray at the lower dose rate to that at t he higher dose rate, was 3.25 for frequency of micronuclei and was eve n higher (4.57) for micronuclei per cell (P < 0.05). Since the differe nces in exposure time for the different dose rates are not large, our results cannot be explained by the differential effect on cell kinetic s during tumor irradiation. However, it cannot be excluded that the di fferential effect of radiation on division delay and redistribution of cells in the phases of the cell cycle may be expressed during incubat ion of cells in vitro for micronucleus expression. Furthermore, it can be hypothesized that more cells may die in culture because of interph ase death and apoptosis in the higher dose-rate group than in the lowe r dose-rate group and that these cells were not accessible for the mic ronucleus assay. The actual explanation for the phenomenon observed re quires further experimentation. (C) 1998 by Radiation Research Society .