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Lethality of Nogalamycin, Nogalamycin Analogs, and Adriamycin to Cells in Different Cell Cycle Phases¹

Cancer Research, The Upjohn Company, Kalamazoo, Michigan 49001

The drugs studied included nogalamycin and its derivative 7-con-O-methylnogalarol, dis-nogamycin and its derivative 7-con-O-methylnogarol, and Adriamycin. All of these drugs, especially at high doses, were lethal to cells in every phase of the cell cycle, indicating that they were not phase specific. However, there were significant differences in drug sensitivity of cells in different parts of the cell cycle.

Nogalamycin and Adriamycin were most lethal to the cells in S phase, whereas cells in M, G₁, and G₂ were much less sensitive. In contrast, the nogalamycin derivative 7-con-O-methylnogalarol was almost equally lethal to cells in all phases of the cell cycle.

dis-nogamycin was most lethal to cells in postmetaphase and in early S phase. Cells in mid- and late G₁, late S, and G₂ were much less sensitive.

The pattern of sensitivity of 7-con-O-methylnogarol was different from that of dis-nogamycin. 7-con-O-Methylnogarol was most lethal to cells in early G₁, S, and G₂. Only cells in mid- and late G₁ were much less sensitive to this drug.

¹ This study was supported in part by Contract NO1-CM-43753, Division of Cancer Treatment, NCI, NIH, Department of Health, Education, and Welfare.

² To whom requests for reprints should be addressed.

Received 8/29/79. Accepted 6/19/80.