Bleomycin-induced Damage in Prematurely Condensed Chromosomes and Its Relationship to Cell Cycle Progression in CHO Cells

The phenomenon of premature chromosome condensation, which involves the fusion of mitotic with interphase cells, was applied to the study of bleomycin-induced chromosome damage in Chinese hamster ovary cells. Examination of the prematurely condensed chromosomes immediately after bleomycin treatment revealed a 5 to 9 times higher incidence of chromosome aberrations than the incidence observed in mitotic chromosomes. Attempts to understand the cause for the existence of such a wide difference between prematurely condensed and mitotic chromosomes revealed the following: (a) bleomycin treatment (25 μg/ml for 30 min) had no effect on the progression of cells from mitosis to G₁or from G₁to S; (b) the rate of progression of S and G₂ phase cells into mitosis was slower in the treatment than in the control; (c) nearly one-half (44%) of the G₂ cells failed to enter mitosis even at 7 hr after the treatment; (d) about one-third of the aberrations (gaps and breaks) observed in the prematurely condensed chromosomes were repaired within 60 min after treatment. There was an indication that cells with extensive chromosome damage failed to enter mitosis, and hence they were blocked in G₂ until the damage was repaired to tolerable levels. The data also suggested the existence of a maximum limit for the amount of chromosome damage that a cell can carry and still enter mitosis.