FURTHER CHARACTERIZATION OF THE RADIOSENSITIVITY OF THE SCID MOUSE

Purpose: To further characterize the radiation response of the scid mu tation. Materials and methods: X-ray induced chromosomal aberrations a nd cell killing were analysed using various in vivo or in vitro cell s ystems. Results: Using low LET X-irradiation a reverse dose-rate effec t was found for killing of differentiated and differentiating spermato gonia and the chromosomal hyperradiosensitivity of scid mice was exten ded to the meiotic prophase. Most striking was the observation made in vitro with synchronized established cell lines that, contrary to the situation in wild-type cells, scid cells display high levels of both c hromatid- and chromosome type aberrations when irradiated during the G (1)-phase of the cell cycle. A timecourse for induction of micronuclea ted polychromatic erythrocytes (MPCE) was determined for scid mice usi ng flow analysis. No significant differences with wild-type mice were recorded. The chromosomal radiosensitivity at the G(1) stage in scid c ells was 4.3 times higher than in control CB-17 cells whereas G(2) sen sitivity differed only by a factor of 1.3. Conclusions: The reportedly normal radiosensitivity for MPCE in scid mice together with previous findings of hypo- or normal radiation sensitivity of scid cells could be explained by the induction of highly lethal chromatid-type damage a t the G(1) stage of the cell cycle leading to selective elimination of aberration-carrying cells. The differences in chromosomal radiosensit ivity between wild-type and scid for the G(1) and G(2) Stage of the ce ll cycle correlate with variation in the rates of DNA double-strand br eak (dsb) repair in scid cells during the cell cycle found by others.