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Cell Cycle Dependency of DNA Damage and Repair in Transformable Mouse Fibroblasts Treated with N-Methyl-N'-nitro-N-nitrosoguanidine¹

McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

Alkaline sucrose sedimentation procedures were used to study the repair of DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) over the range of doses that were from 10 to 99% lethal in transformable mouse fibroblasts (C3H/10T1/2 CL8 cells), which were synchronized by arginine deprivation. Repair occurred at a rapid rate in cells treated 4 hr before (I) or shortly after (II) the commencement of DNA synthesis. However, in cells treated when DNA synthesis was blocked (III), no repair could be detected until after the block was released. By contrast, II was most sensitive, while I and III were equally sensitive to lethality induced by MNNG. Furthermore, the previously demonstrated peak of oncogenic transformation produced by MNNG occurred in I, whereas II, which exhibited an equally rapid rate of repair, was not transformed so readily. It was concluded that in this system there is no direct correlation between DNA repair, as measured by alkaline sucrose sedimentation, and susceptibility to transformation or lethality produced by MNNG.

¹ This work was supported in part by Grant CA 7175 from the National Cancer Institute, NIH, and Grant BC-2C from the American Cancer Society.

² American Cancer Society Professor of Oncology.

Received 12/ 3/73. Accepted 3/11/74.