EFFECT OF DNA-DAMAGING AGENTS ON DNA REPLICATION AND CELL-CYCLE PROGRESSION OF CULTURED MOUSE MAMMARY CARCINOMA CELLS

The effects of DNA-crosslinking agents (mitomycin C and cisplatin), a DNA-intercalating agent (adriamycin) and monofunctional psoralen adducts (4-methyl-4', 5'-dihydropsoralen plus near-UV radiation or 8-methoxypsoralen plus narrow band 395nm light) on DNA replication and cell-cycle progression of cultured mouse mammary carcinoma cells were studied and compared at a dose of each agent sufficient to cause complete inhibition of cell growth. In cells treated with the DNA-crosslinking agents, inhibition of incorporation of [3H]thymidine occurred progressively upon incubation of the treated cells, and finally the cells were arrested at the G2 phase. However, although the mode of inhibition of DNA replication or cell-cycle traverse was the same as that of the crosslinking agents, adriamycin did not completely block cell progression at the G2 phase and some of the cells entered the G1 phase. In contrast to these agents, monofunctional psoralen adducts inhibited DNA replication immediately after treatment and no shift in the distribution of cells in the cell-cycle was observed during incubation. These results suggested different responses of the cells to different types of DNA damage.