The effect of 125I decay at different stages of S-phase on survival, expression of micronuclei and chromosome aberrations in CHO cells

Abstract

Chinese hamster ovary (CHO) cells were synchronized in M phase by mitotic selection, and then re-synchronized with aphidicolin at the G1/S phase border. The cells were labelled in early-S phase by 10 min exposure to 125I-iododeoxyuridine and then cultured (chased) in non-radioactive medium for 0.5, 3 or 5h, followed by harvesting and freezing to accumulate the desired number of 125I decays. Cell damage was assessed by evaluating colony formation, micronucleus formation and chromosome aberrations. These biological estimators of damage showed that the cytocidal effect of 125I decay increased with the duration of the post-labelling chase period: the highest level of damage was found in cells from the 5 h chase period and the lowest in the cells from the 0.5 h chase period. Survival curves for the three chase periods displayed low-dose hyper-radiosensitivity for 0 to 20 125I decays cell-1. The results indicate that the repair of DNA double-strand breaks (DSBs) may depend on the maturation stage of chromatin and an explanation of this finding is proposed which invokes the homologous recombination model for DSB repair.

ICRU REPORT 96, Dosimetry-Guided Radiopharmaceutical Therapy

“…It has been shown that the high-LET-type damage caused by 125 IUdR is highly dependent on when the decay takes place during the cell cycle. Specifically, the precise time the decay takes place after pulse labeling with 125 IUdR at the G1/S boundary has a profound impact on its radiotoxicity (Ludwikow et al , 1996). The decays that occurred early in S-phase produced low-LET-type damage (shouldered survival curve), whereas those that occurred in late S-phase produced high-LET-type damage (no shoulder).…”