title: Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells.
abstract: 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.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Laboratory for Health Protection Research (GBO), NL-3720 BA Bilthoven, the Netherlands.
authors.forename: Anuska G
authors.initials: AG
authors.lastname: Mahabir
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: Schaap
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.forename: Jan
authors.initials: J
authors.lastname: van Benthem
authors.forename: Coenraad F M
authors.initials: CF
authors.lastname: Hendriksen
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
mesh_terms: 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
chemical_list: D009153:Mutagens; D001761:Bleomycin; D016685:Mitomycin; D000099:Acetoxyacetylaminofluorene; D005038:Ethylnitrosourea