TARGETS FOR RADIATION-INDUCED CELL-DEATH - TARGET REPLICATION DURING THE CELL-CYCLE EVALUATED IN CELLS EXPOSED TO X-RAYS OR I-125 DECAYS

Chinese hamster ovary cells were labelled with I-125-iododeoxyuridine (1.15x10(3) Bq/ml) for 12 h, then synchronized by mitotic selection, p lated for cell cycle traverse, and harvested during successive stages of the cell cycle for freezing and accumulation of I-125 decays. Cell viability was evaluated by the colony-forming assay. Cells subjected t o I-125 decays during the G1 phase exhibited exponential survival curv es with an N=1 and a D0=38-41 decays/cell. A continuous increase in I- 125 resistance was observed as cells progressed through the S phase an d cells in late-S/G2 yielded shouldered survival curves with a N=2 and a D0=78-84 decays/cell. After mitosis, the radiation resistance of ce lls returned to G1 values. These findings suggest that the primary tar get for radiation-induced cell death is duplicated during S phase, wit h G1 cells containing one target and G2 cells two targets. Dual target s, although located within a single cell, act as independent entities as if already distributed between two separate daughter cells. Therefo re, the colony-forming assay provides survival values representative o f single cells/single targets only for cells irradiated during the G1 phase of the cell cycle. For cells irradiated in S or G2 phases, when intracellular target multiplicity > 1, the colony-forming assay system atically gives higher values of cell survival by up to 100% due to the target multiplicity. Experiments with external X-rays confirm these c onclusions.