Analysis Tools
cellular
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• cultured mouse embryonic fibroblasts (MEFs) show an increased percentage of chromosomal aberrations compared to all other genotypes; by the third passage, 48% of metaphase spreads show at least one abnormality, while 32% have multiple abnormalities
• in vivo, mice show an elevated level of chromosomal instability compared to controls
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• cells show reduced viability in response to treatment with amphidicolin; cells are 5-fold more sensitive to the replication inhibitor than Hus1tm1Led /+ cells
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• after BPDE treatment, DNA synthesis is maintained at 79.4% of untreated controls cultures, while Hus1tm1Led/+ cultures show a reduction of DNA synthesis to 61.9% of control; this indicates that the S-phase damage checkpoint inhibiting DNA synthesis in response to genome damage is decreased in effectiveness
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• MEFs from mutants show severely limited growth capacity compared to wild-type MEFs
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• MEFs show a greater accumulation of double strand breaks after amphidicolin treatment than control cells with increased levels of chromatid interchanges
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• MEFs show significantly increased sensitivity to DNA lesion-inducing agent BPDE; only 18.8% of cells remain viable 72 hours after treatment compared to 46% of heterozygous cells
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• treatment of cells with an antioxidant (NAC) almost completely suppresses the premature senescence
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