The Nature of Adriamycin-Induced Cytotoxicity in Chinese Hamster Cells as Revealed by Premature Chromosome Condensation

The short-and long-term effects of adriamycin treatment on the cell cycle kinetics and chromosome structure of Chinese hamster ovary cells were investigated. Adriamycin treatment, either pulse or continuous, did not delay the progression of G 1 cells into S phase but did prolong the duration of S and G 2 phases. This effect was dose dependent, and the prolongation of G 2 period was greater than that of S. The frequency of chromosomal aberrations induced by adriamycin was studied in the mitotic as well as in the prematurely condensed chromosomes (PCC) of the treated cells. The types of aberrations observed were chromosome stickiness, chromatid exchanges, breaks, and gaps. The frequency of aberrations continued to increase as cells progressed to mitosis even after the removal of drug from the medium. At prolonged intervals (24 to 72 hr) after a brief or extended treatment, the labeling indices of the treated populations decreased, indicating an eventual block in the cell cycle progression. Visualization of chromosomes of these blocked interphase cells by the PCC method revealed that normal G 2 PCC were totally absent. We observed that the PCC of these blocked cells were abnormal in the following respects: (a) some of the G 2 PCC were extensively damaged; (b) many of the S PCC failed to incorporate [3 H]thymidine; (c) a significant fraction of these PCC were poorly condensed and hence it was difficult to determine whether they were in G 1 or G 2. These results indicate that there is a good correlation between damage to the genome and the inhibition of cell cycle progression after adriamycin treatment.