Further characterization of the radiosensitivity of the scid mouse.
OBJECTIVE
To further characterize the radiation response of the scid mutation.


METHODS
X-ray induced chromosomal aberrations and cell killing were analysed using various in vivo or in vitro cell systems.


RESULTS
Using low LET X-irradiation a reverse dose-rate effect was found for killing of differentiated and differentiating spermatogonia and the chromosomal hyperradiosensitivity of scid mice was extended 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 chromatid- and chromosome type aberrations when irradiated during the G1-phase of the cell cycle. A time-course for induction of micronucleated polychromatic erythrocytes (MPCE) was determined for scid mice using flow analysis. No significant differences with wild-type mice were recorded. The chromosomal radiosensitivity at the G1 stage in scid cells was 4.3 times higher than in control CB-17 cells whereas G2 sensitivity 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 at the G1 stage of the cell cycle leading to selective elimination of aberration-carrying cells. The differences in chromosomal radiosensitivity between wild-type and scid for the G1 and G2 stage of the cell cycle correlate with variation in the rates of DNA double-strand break (dsb) repair in scid cells during the cell cycle found by others.
MGC-Department of Radiation Genetics and Chemical Mutagenesis Sylvius Laboratory, Leiden University, Netherlands.
P P
PP
van Buul
L
L
Abramsson-Zetterberg
I M
IM
Zandman
A
A
van Duyn-Goedhart
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000235:genetics; D002875:Chromosomes / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000473:pathology / Q000528:radiation effects; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000528:radiation effects; D007399:Interphase / Q000528:radiation effects; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000235:genetics*; D048629:Micronuclei, Chromosome-Defective / Q000473:pathology / Q000528:radiation effects; D011836:Radiation Tolerance / Q000235:genetics*; D013093:Spermatogonia / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects; D014965:X-Rays / Q000009:adverse effects