Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells.
BACKGROUND
Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC) as compared to wild-type (WT) cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM) and gamma-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts) after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls.


RESULTS
Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments.


CONCLUSIONS
These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.
Mahabir
Anuska G
AG
National Institute for Public Health and the Environment (RIVM), Laboratory for Health Protection Research (GBO), NL-3720 BA Bilthoven, the Netherlands.
Schaap
Mirjam M
MM
Pennings
Jeroen L A
JL
van Benthem
Jan
J
Hendriksen
Coenraad F M
CF
van Steeg
Harry
H
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001761:Bleomycin / Q000494:pharmacology*; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D005038:Ethylnitrosourea / Q000494:pharmacology; D020869:Gene Expression Profiling; D005838:Genotype; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D009153:Mutagens / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis
D009153:Mutagens; D001761:Bleomycin; D016685:Mitomycin; D000099:Acetoxyacetylaminofluorene; D005038:Ethylnitrosourea