DNA-repair-deficient Rad54/Rad54B mice are more sensitive to clastogens than wild-type mice.
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| Abstract |
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 gamma-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 gamma-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.
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| Authors | Anuska G Mahabir, Mirjam Schaap, Peter Theunissen, Jan van Benthem, Jeroen Essers, Annemieke de Vries, Coenraad F M Hendriksen, Harry van Steeg |
| Journal | Toxicology letters (Toxicol Lett) Vol. 183 Issue 1-3 Pg. 112-7 (Dec 15 2008) ISSN: 0378-4274 [Print] Netherlands |
| PMID | 19007869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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