DNA-repair-deficient Rad54/Rad54B mice are more sensitive to clastogens than wild-type mice.
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.
Mahabir
Anuska G
AG
National Institute for Public Health and the Environment (RIVM), Laboratory for Health Protection Research, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands.
Schaap
Mirjam
M
Theunissen
Peter
P
van Benthem
Jan
J
Essers
Jeroen
J
de Vries
Annemieke
A
Hendriksen
Coenraad F M
CF
van Steeg
Harry
H
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005720:Gamma Rays; D005838:Genotype; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015162:Micronucleus Tests / Q000379:methods; D016685:Mitomycin / Q000633:toxicity; D016296:Mutagenesis / Q000187:drug effects / Q000528:radiation effects; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*
D009153:Mutagens; D009687:Nuclear Proteins; D001761:Bleomycin; D016685:Mitomycin; D004265:DNA Helicases; C103534:Rad54l protein, mouse; D005038:Ethylnitrosourea