THE RELATIONSHIP BETWEEN P53 STATUS, DNA-REPAIR AND CHROMATID ABERRATION INDUCTION IN G(2) MOUSE EMBRYO FIBROBLAST CELLS TREATED WITH BLEOMYCIN

The involvement of p53 in the formation of chromosome aberrations was assessed by analyzing bleomycin-induced, chromatid-type aberrations in G(2) phase fibroblasts derived from embryos from wild-type and p53 kn ock-out mice. Cells that were p53+/- or p53-/- were more sensitive to the induction of aberrations than the p53+/+ cells, particularly at co ncentrations of 7.5 and 10.0 mu g/ml. The p53-deficient cells also sho wed an overdispersed distribution of bleomycin-induced chromatid aberr ations, a greater amount of overall genomic instability and a possible loss of a cell death pathway. These data are interpreted as indicatin g a role for p53 in DNA repair in the Gz phase, with a loss of p53 lea ding to an increased frequency of deletions (incomplete repair) and in terchanges (misrepair). The specific role remains to he elucidated. Th e mitotic index decreased with increasing bleomycin concentration to a similar extent in all three cell lines, indicating that the loss of a Ga checkpoint in p53-/- and p53 +/- cells was not an explanation for the increased sensitivities in these cells compared with the p53 +/+.