The sensitivity of DNA-repair-deficient Rad54/Rad54B mice for clastogens was studied and compared to that of wild-type mice. LacZ mutant frequencies (MF) in Rad54/Rad54B mice, after treatment with mitomycin C (MMC), bleomycin (BLM) and γ-irradiation, were compared to those of the wild-type mice following the same treatments. While none of the clastogens showed an induction of the lacZ MF in the wild-type mice, there was a significant increase of the lacZ MF in the bone marrow of the Rad54/Rad54B mice after treatment with BLM and γ-irradiation and in the spleen after MMC treatment. As expected, the positive control ENU showed a significant increase in the lacZ MF in all tested organs in wild-type mice. Mutant colonies were hybridized with total mouse DNA in order to discriminate between small gene mutations and large DNA rearrangements and translocations (size-change mutations). The hybridization studies showed a significant increase in mouse DNA positive clones 4 days after treatment with MMC and BLM in the bone marrow of the wild-type mice, which is indicative for chromosomal rearrangements and translocations to occur. An even more pronounced increase was seen 28 days after treatment with the same compounds in the Rad54/Rad54B mice.

Chromosomal rearrangements, Clastogens, DNA-repair, Double-strand breaks, LacZ mutant frequencies,
Toxicology Letters
Erasmus MC: University Medical Center Rotterdam

Mahabir, A.G, Schaap, M, Theunissen, P, van Benthem, J, Essers, J, de Vries, A, … van Steeg, H. (2008). DNA-repair-deficient Rad54/Rad54B mice are more sensitive to clastogens than wild-type mice. Toxicology Letters, 183(1-3), 112–117. doi:10.1016/j.toxlet.2008.10.005